elastin and Thrombosis

Platelets are essential mediators of inflammation and thrombosis. Chronic obstructive pulmonary disease (COPD) is a heterogeneous multisystem disease, causing significant morbidity and mortality worldwide. Recent evidence suggests that the lung is an important organ for platelet biogenesis. Cigarette smoking has been shown to induce platelet aggregation and decrease the capacity of mitochondrial electron transport system in platelets. Preclinical and clinical studies have suggested that platelets may contribute to the development of COPD through the breakdown of lung elastin by platelet factor 4, platelet activation and formation of platelet aggregates, and modulation of hypoxia signaling pathways. Recent large population studies have produced encouraging results indicating a potential role for aspirin in preventing exacerbations and delaying disease progression in patients with COPD. This review summarizes the information about the lung as an organ for platelet production, pathophysiological functions of platelets and platelet mediators in the development of COPD, and the most updated evidence on the utility of aspirin in patients with COPD.

Topics: Aspirin; Blood Platelets; Disease Progression; Elastin; Electron Transport; Humans; Inflammation; Lung; Megakaryocytes; Mitochondria; Mitochondrial Diseases; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Factor 4; Pulmonary Disease, Chronic Obstructive; Smoking; Thrombosis

Surface-induced thrombosis is a significant issue for artificial blood-contacting materials used in the treatment of cardiovascular diseases. The development of biomaterials and tissue-engineered constructs that mimic the vasculature represents a way to overcome this problem. Elastin is an extracellular matrix macromolecule that imparts arterial elasticity where it comprises up to 50% of the nonhydrated mass of the vessel. In addition to its critical role in maintaining vessel integrity and elastic properties under pulsatile flow, elastin plays an important role in signaling and regulating luminal endothelial cells and smooth muscle cells in the arterial wall. Despite its well-established significance in the vasculature and its growing use as a biomaterial in tissue engineering, the hemocompatibility of elastin is often overlooked. Past studies pointing to the potential of arterial elastin and decellularized elastin as nonthrombogenic materials have begun to be realized, with elastin scaffolds and coatings displaying increased hemocomptibility. This review explores the mechanisms of elastin's nonthrombogenicity and highlights the current problems limiting its wider application as a biomaterial. We discuss the benefits of constructing biomaterials encompassing the relevant mechanical and biological features of elastin to provide enhanced hemocompatibility to biomaterials.

Topics: Animals; Biocompatible Materials; Blood Coagulation; Blood Platelets; Blood Vessels; Elasticity; Elastin; Endothelial Cells; Humans; Models, Biological; Myocytes, Smooth Muscle; Peptides; Thrombosis; Tissue Engineering

The development of a clinically durable small-diameter vascular graft as well as permanently implantable biosensors and artificial organ systems that interface with blood, including the artificial heart, kidney, liver, and lung, remain limited by surface-induced thrombotic responses. Recent breakthroughs in materials science, along with a growing understanding of the molecular events that underlay thrombosis, has led to the design and clinical evaluation of a variety of biologically active coatings that inhibit components of the coagulation pathway and platelet responses by surface immobilization or controlled release of bioactive agents. This report reviews recent progress in generating synthetic thromboresistant surfaces that inhibit (1) protein and cell adsorption, (2) thrombin and fibrin formation, and (3) platelet activation and aggregation.

Topics: Albumins; Animals; Anticoagulants; Biocompatible Materials; Blood Coagulation; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Carbon; Elastin; Fibrin; Heparin; Humans; Nitric Oxide Donors; Phosphorylcholine; Platelet Activation; Platelet Aggregation Inhibitors; Polyethylene Glycols; Prosthesis Design; Stents; Thrombin; Thrombomodulin; Thrombosis

Biomaterials, including non-biodegradable and biodegradable polymers, and collagen and fibrin matrices, have been used in experimental and clinical arterial reconstruction. While these biomaterials exhibit various characteristics suitable for arterial reconstruction, the patency of biomaterial-based arterial substitutes remains problematic because of inflammation and thrombogenesis. Endothelial cell seeding of biomaterials has been proposed and used for reducing the thrombogenicity of biomaterials. However, difficulties in cell retention hamper the application of such an approach. Although autogenous vein grafts offer satisfactory results, not all patients possess veins available for arterial replacements. Thus, a critical issue in arterial reconstruction is developing arterial substitutes that are inflammation/thrombosis-resistant while possessing the characteristics of natural arteries. Here we show that allogenic vascular elastic laminae exhibit anti-inflammatory properties and may be considered a potential material for arterial reconstruction. In this article, we briefly review the composition, structure, and function of vascular elastic laminae, summarize recent discoveries on the role of elastic laminae in regulating leukocyte adhesion and vascular smooth muscle cell proliferation and migration, and discuss potential applications of allogenic elastic laminae to arterial reconstruction.

Topics: Angioplasty; Animals; Biocompatible Materials; Blood Vessel Prosthesis; Blood Vessels; Cell Adhesion; Cell Movement; Cell Proliferation; Elastin; Endothelium, Vascular; Gene Expression Regulation; Humans; Inflammation; Leukocytes; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Polymers; Thrombosis

This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesions progression. The initial (type I) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

Topics: Aneurysm; Arteriosclerosis; Blood Vessels; Calcium; Collagen; Coronary Artery Disease; Coronary Vessels; Elastin; Extracellular Matrix; Fibrinogen; Foam Cells; Humans; Lipid Metabolism; Lipoproteins; Lymphocytes; Muscle, Smooth, Vascular; Proteoglycans; Thrombosis; Tunica Intima

Topics: Animals; Arteriosclerosis; Aspirin; Blood Platelets; Cell Division; Collagen; Coronary Artery Bypass; Dipyridamole; Elastin; Endothelium; Graft Occlusion, Vascular; Hemodynamics; Humans; Lipoproteins; Models, Cardiovascular; Muscle, Smooth, Vascular; Risk; Saphenous Vein; Thrombosis

In studies concerning risk factors for cardiovascular diseases, a number of reports have emphasized the influence of lipids, but the role of dietary minerals other than sodium has been less studied. However, epidemiological studies have suggested that dietary intake of magnesium and potassium may be involved in such pathogenesis. Studies of the influence of magnesium deficiency on arteriosclerosis include its effect on the initial lesion, altered metabolism of elastin, proliferation of collagen, calcification, lipid metabolism, platelet aggregation and hypertension. Magnesium and potassium metabolism are closely related and magnesium is required for maintaining the level of cellular potassium. As a consequence, magnesium and potassium deficiency frequently occur together and potassium deficiency may be an aggravating factor in pathogenesis. The development of the initial lesion in the arterial wall may be facilitated by loss of cellular magnesium and potassium. Experimental magnesium deficiency induces arterial damage, a loss of magnesium and potassium and an increase in the calcium and sodium content of the cell. Experimental models that have been used to produce cardiovascular lesions induce similar changes and losses of major intracellular cations may affect the main metabolic processes of the cell. This report summarizes the experimental evidence that magnesium deficiency may affect several different stages involved in arteriosclerosis and that potassium deficiency may exacerbate this. Magnesium deficiency results in vascular calcification. Experiments indicate that elastin is the site of the initial calcification and the metabolism of elastin is altered. This vascular lesion then brings about an increase in the collagen content of the wall. Low magnesium status could probably affect this process by slowing collagen resorption and lead to an irreversible accumulation of connective tissue. Results showing a different distribution of the various types of lipoprotein during experimental magnesium deficiency strongly suggest that lipid exchange between the vessel walls and blood can be modified. Severe magnesium deficiency in weanling rats produces a marked hypertriglyceridemia, a decrease in the percentage of cholesterol transported by HDL lipoprotein and a reduction in LCAT activity. The decreased clearance of circulatory triglycerides appears to be the major mechanism contributing to hyperlipemia. Magnesium deficiency could therefore contribute to accu

Topics: Animals; Arteriosclerosis; Blood Platelets; Calcinosis; Collagen; Diabetes Mellitus; Diet; Elastin; Humans; Hypertension; Lipid Metabolism; Lipoproteins; Magnesium; Magnesium Deficiency; Muscle, Smooth, Vascular; Potassium; Potassium Deficiency; Rats; Thrombosis

Topics: Aging; Animals; Aorta; Arteriosclerosis; Collagen; Coronary Vessels; Elastic Tissue; Elastin; Humans; Protein-Lysine 6-Oxidase; Pyridoxine; Thrombosis

Two subendothelial structures, glomerular basement membrane and arterial subendothelium, were compared regarding their biochemistry and ultrastructure and their role in physiology and pathology. Filtration function of the glomerular basement membrane can be related to the presence of three layers which are superimposed on each other and which differ regarding the orientation and density of the microfibrils. The arterial subendothelium which is a mixture of amorphous material, microfibrilis, elastin and collagen, with a still unknown orientation of these components, limits the transport of many blood molecules and reinforces the endothelial barrier. A striking difference is observed in the thrombogenicity of these two structures, especially in their reactivity towards platelets. This can be related to the presence of collagen IV in the glomerular basement membrane and of collagen III in the arterial subendothelium: in both cases adhesion of platelets can be observed. The presence of platelet aggregates on the subendothelial surface may also be seen. This is probably due to the presence of collagen III which is known to be able to induce the platelet release reaction and thereby promotes aggregation.

Topics: Animals; Aorta; Basement Membrane; Blood Platelets; Collagen; Cytoplasmic Granules; Elastin; Endothelium; Fibrin; Glycoproteins; Glycosaminoglycans; Humans; Kidney Glomerulus; Lipids; Microscopy, Electron; Permeability; Platelet Adhesiveness; Thrombosis

Topics: Animals; Arteries; Basement Membrane; Blood Coagulation; Connective Tissue; Culture Techniques; Elastin; Endothelium; Epithelial Cells; Fibrin; Haplorhini; Hemostasis; Macaca; Microbial Collagenase; Microscopy, Electron; Platelet Adhesiveness; Rabbits; Regeneration; Thrombosis

Topics: Arteries; Arteriosclerosis; Cholesterol; Collagen; Elastin; Glycosaminoglycans; Humans; Hypertension; L-Lactate Dehydrogenase; Macromolecular Substances; Metabolic Diseases; Necrosis; Oxidoreductases; Sclerosis; Thrombosis; Time Factors; Vasa Vasorum

The aim of the study was to determine whether magnetic resonance imaging (MRI) can be used in assessment of biologic activity of intraluminal thrombus (ILT) and proteolytic processes of the abdominal aortic aneurysm wall.. Using MRI, 50 patients with asymptomatic infrarenal abdominal aortic aneurysm were analyzed at the maximum aneurysm diameter on T1-weighted images in the arterial phase after administration of contrast material. Relative ILT signal intensity (SI) was determined as the ratio between ILT SI and psoas muscle SI. During surgery, the full thickness of the ILT and the adjacent part of the aneurysm wall were harvested at the maximal diameter for biochemical analysis. The concentrations of matrix metalloproteinase 9 and neutrophil elastase (NE/ELA) were analyzed in harvested thrombi, and the concentrations of collagen type III, elastin, and proteoglycans were analyzed in harvested aneurysm walls.. A significant positive correlation was found between the NE/ELA concentration of the ILT and the relative SI (ρ = 0.309; P = .029). Furthermore, a negative correlation was observed between the elastin content of the aneurysm wall and the relative SI (ρ = -0.300; P = .034). No correlations were found between relative SI and concentration of matrix metalloproteinase 9, NE/ELA, collagen type III, or proteoglycan 4 in the aneurysm wall.. These findings indicate a potential novel use of MRI in prediction of thrombus proteolytic enzyme concentrations and the extracellular matrix content of the aneurysm wall, thus providing additional information for the risk of potential aneurysm rupture.

Topics: Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Collagen Type III; Cross-Sectional Studies; Elastin; Female; Humans; Leukocyte Elastase; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 9; Middle Aged; Predictive Value of Tests; Proteoglycans; Proteolysis; Thrombosis

To date, clinically available expanded polytetrafluoro-ethylene (ePTFE) vascular grafts are suboptimal for reconstructing small caliber (D < 6 mm) arteries, owing to thrombosis in early and restenosis in late stage. Our aim in this preliminary study was to fabricate a nano-fibrous vascular graft which was biofunctionalized with VEGF. Four-mm caliber grafts were prepared by the coaxial-elctrospun technique, which consisted of poly(l-lactide-co-caprolactone) [P(LLA-CL)] collagen and elastin. Heparin and endothelial cell growth factor-165 (VEGF. Biofunctionalized electrospun graft showed surgical properties, hemocompatibility and higher short-term patency compared with the ePTFE grafts. Despite good early performances, profound study should be designed for long-term evaluation.

Topics: Animals; Anticoagulants; Aorta, Abdominal; Biocompatible Materials; Blood Vessel Prosthesis; Collagen; Elastin; Endothelial Cells; Heparin; Polyesters; Postoperative Complications; Rabbits; Thrombosis; Vascular Endothelial Growth Factor A; Vascular Grafting

We explored the use of recently developed gels obtained by the catalyst free click reaction of elastin-like recombinamers (ELRs) to fabricate a new class of covered stents. The approach consists in embedding bare metal stents in the ELR gels by injection molding, followed by endothelialization under dynamic pressure and flow conditions in a bioreactor. The mechanical properties of the gels could be easily tuned by choosing the adequate concentration of the ELR components and their biofunctionality could be tailored by inserting specific sequences (RGD and REDV). The ELR-covered stents exhibited mechanical stability under high flow conditions and could undergo crimping and deployment without damage. The presence of RGD in the ELR used to cover the stent supported full endothelialization in less than 2weeks in vitro. Minimal platelet adhesion and fibrin adsorption were detected after exposure to blood, as shown by immunostaining and scanning electron microscopy. These results prove the potential of this approach towards a new and more effective generation of covered stents which exclude the atherosclerotic plaque from the blood stream and have high biocompatibility, physiological hemocompatibility and reduced response of the immune system.

Topics: Cardiovascular Diseases; Coated Materials, Biocompatible; Elastin; Human Umbilical Vein Endothelial Cells; Humans; Microscopy, Electron, Scanning; Stents; Thrombosis

Thrombus ages, defined as four relative age phases, are related to different compositions of the intraluminal thrombus (ILT) in the abdominal aortic aneurysm (AAA) (Tong et al., 2011b). Experimental studies indicate a correlation between the relative thrombus age and the strength of the thrombus-covered wall.. On 32 AAA samples we performed peeling tests with the aim to dissect the material (i) through the ILT thickness, (ii) within the individual ILT layers and (iii) within the aneurysm wall underneath the thrombus by using two extension rates (1mm/min, 1mm/s). Histological investigations and mass fraction analysis were performed to characterize the dissected morphology, to determine the relative thrombus age, and to quantify dry weight percentages of elastin and collagen in the AAA wall.. A remarkably lower dissection energy was needed to dissect within the individual ILT layers and through the thicknesses of old thrombi. With increasing ILT age the dissection energy of the underlying intima-media composite continuously decreased and the anisotropic dissection properties for that composite vanished. The quantified dissection properties were rate dependent for both tissue types (ILT and wall). Histology showed that single fibrin fibers or smaller protein clots within the ILT generate smooth dissected surfaces during the peeling. There was a notable decrease in mass fraction of elastin within the thrombus-covered intima-media composite with ILT age, whereas no significant change was found for that of collagen.. These findings suggest that intraluminal thrombus aging leads to a higher propensity of dissection for the ILT and the intima-media composite of the aneurysmal wall.

Topics: Aged; Aged, 80 and over; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Dissection; Collagen; Elastin; Endothelium, Vascular; Fibrin; Humans; Middle Aged; Pressure; Thrombosis

Elastin is the major structural extracellular matrix component of the arterial wall that provides the elastic recoil properties and resilience essential for proper vascular function. Elastin-derived peptides (EDP) originating from elastin fragmentation during vascular remodeling have been shown to play an important role in cell physiology and development of cardiovascular diseases. However, their involvement in thrombosis has been unexplored to date. In this study, we investigated the effects of EDP on (1) platelet aggregation and related signaling and (2) thrombus formation. We also characterized the mechanism by which EDP regulate thrombosis.. We show that EDP, derived from organo-alkaline hydrolysate of bovine insoluble elastin (kappa-elastin), decrease human platelet aggregation in whole blood induced by weak and strong agonists, such as ADP, epinephrine, arachidonic acid, collagen, TRAP, and U46619. In a mouse whole blood perfusion assay over a collagen matrix, kappa-elastin and VGVAPG, the canonical peptide recognizing the elastin receptor complex, significantly decrease thrombus formation under arterial shear conditions. We confirmed these results in vivo by demonstrating that both kappa-elastin and VGVAPG significantly prolonged the time for complete arteriole occlusion in a mouse model of thrombosis and increased tail bleeding times. Finally, we demonstrate that the regulatory role of EDP on thrombosis relies on platelets that express a functional elastin receptor complex and on the ability of EDP to disrupt plasma von Willebrand factor interaction with collagen.. These results highlight the complex nature of the mechanisms governing thrombus formation and reveal an unsuspected regulatory role for circulating EDP in thrombosis.

Topics: Animals; Blood Platelets; Cathepsin A; Cattle; Collagen; Elastin; Humans; Mice; Neuraminidase; Oligopeptides; Peptide Fragments; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Proteolysis; Receptors, Cell Surface; Signal Transduction; Thrombosis; Vascular Remodeling; von Willebrand Factor

Abdominal aortic aneurysm (AAA) is a serious disease due to its covert nature, relatively high prevalence and fatal prognosis in the case of rupture. To obtain new insights into AAA pathogenesis, we examined the relationships between histopathology, multiplex in vitro immunoassay data, diameter and symptomatology.. In a prospective, non-randomised study, we evaluated samples from 6 normal infrarenal aortae and 65 AAA patients (65 walls, 55 thrombi). The AAA patients were either asymptomatic (n = 44), symptomatic (n = 7) or with ruptured AAA (n = 14). The AAA diameter was classified as small (<5 cm, n = 18), medium (5-7 cm, n = 26) and large (>7 cm, n = 21). We quantified the histopathology of the AAA wall and the adjacent thrombus. We assessed the expression of proteins in the same samples.. Asymptomatic AAAs had walls with more abundant inflammatory infiltrates, lower amounts of PAI-1, a higher number of tPA-positive elements, a tendency towards decreased collagen content, whereas the adjacent thrombi had a greater concentration of VCAM-1 and MMP-2 when compared with symptomatic AAAs. Compared with the aneurysmatic aorta, the normal aorta contained less collagen and more elastin, actin, desmin and PAI-1-positive elements; in addition, it was more vascular. Medium-sized AAAs were the most actin and vimentin rich, and large AAAs were the most vascular.. Our results show that asymptomatic AAA walls often have more potentially deleterious histopathological alterations than symptomatic AAA walls. This result indicates that a progression from an asymptomatic AAA to rupture can be expected and screening patients who are at risk of rupture could be beneficial.

Topics: Actins; Adult; Aged; Aged, 80 and over; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Rupture; Asymptomatic Diseases; Collagen; Desmin; Disease Progression; Elastin; Extracellular Matrix; Female; Histocytochemistry; Humans; Male; Matrix Metalloproteinase 2; Middle Aged; Plasminogen Activator Inhibitor 1; Prospective Studies; Thrombosis; Vascular Cell Adhesion Molecule-1

An association of intraluminal thrombus (ILT) with abdominal aortic aneurysm (AAA) growth has been suggested. Previous in vitro experiments have demonstrated that aneurysm-associated thrombus may secrete proteolytic enzymes and may develop local hypoxia that might lead to the formation of tissue-damaging reactive oxygen species. In this study, we assessed the hypothesis that ventral ILT thickness is associated with markers of proteolysis and with lipid oxidation in the underlying AAA vessel wall.. Ventral AAA tissue was collected from asymptomatic patients at the site of maximal diameter during open aneurysm repair. Segments were divided, one part for biochemical measurements and one for histologic analyses. We measured total cathepsin B, cathepsin S levels, and matrix metalloproteinase (MMP)-2 and MMP-9 activity. Myeloperoxidase and thiobarbituric acid reactive substances were determined as measures of lipid oxidation. Histologic segments were analyzed semiquantitatively for the presence of collagen, elastin, vascular smooth muscle cells (VSMCs), and inflammatory cells. Preoperative computed tomography angiography scans of 83 consecutive patients were analyzed. A three-dimensional reconstruction was obtained, and a center lumen line of the aorta was constructed. Ventral ILT thickness was measured in the anteroposterior direction at the level of maximal aneurysm diameter on the orthogonal slices.. Ventral ILT thickness was positively correlated with aortic diameter (r=0.25; P=.02) and with MMP-2 levels (r=0.27; P=.02). No biochemical correlations were observed with MMP-9 activity or cathepsin B and S expression. No correlation between ventral ILT thickness and myeloperoxidase or thiobarbituric acid reactive substances was observed. Ventral ILT thickness was negatively correlated with VSMCs (no staining, 18.5 [interquartile range, 12.0-25.5] mm; minor, 17.6 [10.7-22.1] mm; moderate, 14.5 [4.6-21.7] mm; and heavy, 8.0 [0.0-12.3] mm, respectively; P=.01) and the amount of elastin (no staining, 18.6 [12.2-30.0] mm; minor, 16.5 [9.0-22.1] mm; moderate, 11.7 [2.5-15.3] mm; and heavy 7.7 [0.0-7.7] mm, respectively; P=.01) in the medial aortic layer.. ILT thickness appeared to be associated with VSMCs apoptosis and elastin degradation and was positively associated with MMP-2 concentrations in the underlying wall. This suggests that ILT thickness affects AAA wall stability and might contribute to AAA growth and rupture. ILT thickness was not correlated with markers of lipid oxidation.

Topics: Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Rupture; Aortography; Apoptosis; Biopsy; Cathepsin B; Cathepsins; Collagen; Elastin; Female; Humans; Inflammation; Linear Models; Lipid Peroxidation; Logistic Models; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Multivariate Analysis; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Observer Variation; Peroxidase; Predictive Value of Tests; Reproducibility of Results; Thiobarbituric Acid Reactive Substances; Thrombosis; Tomography, X-Ray Computed

The main purpose of the present study is the investigation of gender differences in the biomechanical properties, thrombus age, mass fraction and key clinical factors of abdominal aortic aneurysms (AAAs).. A total of 90 AAA samples (78 males and 12 females) were harvested from open surgical aneurysm repairs. Biaxial extension and peeling tests were performed to characterise the biaxial mechanical responses and to determine dissection properties of both the intraluminal thrombi (ILTs) and the thrombus-covered walls. Relative thrombus age was determined by characterising the ILT histological microstructure. Mass fraction analyses quantified dry weight percentages of elastin and collagen within the AAA walls. Moreover, we statistically compared clinical factors between male and female.. The luminal layers of the female thrombi and the female AAA walls showed a significantly lower tissue stiffness (modulus) in the longitudinal direction when compared to males. Gender differences were also shown in the dissection properties of the intima-media composite within the AAA walls, in which a statistically significantly lower energy to propagate a dissection was quantified for females than for males. Moreover, 82% of female thrombi were relatively older (ILT age phases III and IV), twice that of male thrombi (43%). A pronounced lower elastin content was identified for the intima-media composites of male AAA walls, whereas female AAA walls had significantly lower dry weight percentages of collagen. Regarding clinical factors, nicotine pack years, serum creatinine and AAA expansion rate were found to be much higher for male patients.. These findings may help to explain higher risks for AAA growth in males and the ruptures of smaller-sized AAAs in females.

Topics: Aged; Aged, 80 and over; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Dissection; Aortic Rupture; Biomechanical Phenomena; Chi-Square Distribution; Collagen; Disease Progression; Elastic Modulus; Elastin; Female; Humans; Male; Middle Aged; Risk Factors; Sex Factors; Thrombosis; Time Factors; Vascular Stiffness

The natural history of abdominal aortic aneurysm (AAA) is wall remodelling potentially leading to a final rupture. The pathogenesis of AAA appears to be multifactorial. The aim of this pilot prospective study was to assess the relationship between the thickness of the thrombus within the abdominal aortic aneurysm, intramural pH and local elastin degradation.. The AAA size, intraluminal thrombus (ILT) morphology and location were evaluated in 206 consecutive patients. Thirty patients with large AAA (aortic diameter > or = 50 mm) and adjacent ILT with the thinnest part < or = 10 mm and thickest > or = 25 mm, measured in the region of the maximum diameter of AAA, were included for further study. During AAA surgery intramural pH measurements were performed and specimens taken from both thin thrombus-covered and thick thrombus-covered wall for computerized morphometric analysis.. Mean intramural pH value was 7.21 +/- 0.18 for the wall covered by thick ILT and 7.64 +/- 0.10 for the thin one (P < 0.001). Computerized morphometric analysis demonstrated that elastin fibres in the thin thrombus-covered wall were decreased in size (for width--P < 0.0001, for length--P < 0.13), irregularly orientated (P < 0.000001) and the amount of fibres was reduced when compared to the wall covered by thick ILT (P < 0.0004).. A strong relationship between intramural pH and elastin net destruction suggests that the local alkaline status within the thin thrombus-covered part of the aneurysm wall is contributing to the elastinolytic process.

Topics: Adult; Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Elastin; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pilot Projects; Radiography; Thrombosis

A recombinant elastin-mimetic triblock protein polymer with an inverse transition temperature (approximately 20 degrees C) was used to impregnate small-diameter (4 mm i.d.) expanded polytetrafluoroethylene (ePTFE) vascular grafts. Scanning electron microscopy confirmed that initial elastin impregnation of the graft followed by further multilayer coating with elastin films filled in the fibril and node structure of the luminal surface of the ePTFE graft and was macroscopically smooth. Elastin protein polymer impregnation reduced the advancing contact angle of the luminal surface to 43 degrees, which was comparable to the advancing contact angle of 47 degrees for a cast elastin film. Attenuated total reflection infrared spectroscopy and Coomassie blue staining revealed little discernable change in the protein surface film after 24 h of shear at 500 s(-1) and 37 degrees C. Excellent short-term blood-contacting properties as determined by minimal fibrin and platelet deposition were demonstrated using a baboon extracorporeal femoral arteriovenous shunt model. The results of this study demonstrate the applicability of an elastin-mimetic triblock protein polymer as a non-thrombogenic coating or as a component of a tissue-engineered composite.

Topics: Acute Disease; Animals; Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis; Coated Materials, Biocompatible; Drug Implants; Elastin; Equipment Failure Analysis; Male; Materials Testing; Papio; Polytetrafluoroethylene; Prosthesis Failure; Protein Binding; Recombinant Proteins; Thrombosis; Treatment Outcome

Surgical therapy of cardiovascular disorders frequently requires replacement of diseased tissues with prosthetic devices or grafts. In typical tissue engineering approaches, scaffolds are utilized to serve as templates to support cell growth and remodeling. Decellularized vascular matrices have been previously investigated as scaffolds for tissue engineering. However, cell migration into these scaffolds was inadequate due to the very tight matrix organization specific to the aortic structure. To address this problem, we prepared two types of decellularized scaffolds from porcine vascular tissues. Pure elastin scaffolds and pure collagen scaffolds were prepared by selectively removing the collagen component or elastin, respectively. In the current study, we use a subdermal implantation model to demonstrate that arterial elastin and collagen scaffolds exhibit enhanced potential for repopulation by host cells in vivo. Notably, numerous new collagen fibers and bundles were found within the remodeled elastin scaffolds and new elastin fibers within collagen scaffolds, respectively, clearly indicating their ability to support de novo extracellular matrix synthesis. We also show that biological cues such as growth factors are required for efficient repopulation of elastin and collagen scaffolds. Finally, we bring evidence that these scaffolds can be endothelialized in vitro for thrombosis resistance and thus can serve as promising candidates for cardiovascular tissue engineering.

Topics: Animals; Arteries; Biocompatible Materials; Blood Platelets; Cell Movement; Collagen; Elastin; Extracellular Matrix; Immunohistochemistry; Models, Biological; Rats; Swine; Thrombosis; Tissue Engineering

Fluorescence emission analysis (FEA) has proven to be very sensitive for the detection of elastin, collagen and lipids, which are recognized as the major sources of autofluorescence in vascular tissues. FEA has also been reported to detect venous thromboemboli. In this paper we have tested the hypothesis that FEA can reproducibly detect in vivo and in vitro triggered plaque disruption and thrombosis in a rabbit model. Fluorescence emission (FE) spectra, recorded in vivo, detected Russell's viper venom (RVV)-induced transformation of atherosclerotic plaque. FE intensity at 410-490 nm 4 weeks after angioplasty was significantly lower (P < 0.0033 by analysis of variance) in RVV-treated rabbits when compared to control animals with stable plaque. FE spectral profile analyses also demonstrated a significant change in curve shape as demonstrated by polynomial regression analysis (R2 from 0.980 to 0.997). We have also demonstrated an excellent correlation between changes in FE intensity and the structural characteristics detected at different stages of "unstable atherosclerotic plaque" development using multiple regression analysis (R2 = 0.989). Thus, FEA applied in vivo is a sensitive and highly informative diagnostic technique for detection of triggered atherosclerotic plaque disruption and related structural changes, associated with plaque transformation, in a rabbit model.

Topics: Angioplasty, Balloon; Animals; Arteriosclerosis; Collagen; Daboia; Disease Models, Animal; Elastin; Fluorescence; Rabbits; Spectrometry, Fluorescence; Thrombosis; Viper Venoms

The intimal hyperplasia hypothesis that equates lumen narrowing after arterial injury with intimal mass has recently been challenged. Evidence has emerged to suggest that lumen narrowing is caused in large part by changes in artery wall geometry rather than intimal mass per se. We have begun to explore this hypothesis in a unique nonhuman primate model of atherosclerosis.. Monkeys who were fed an atherogenic diet for 3 to 5 years underwent experimental angioplasty of the left iliac artery. The contralateral iliac artery served as an intraanimal control. Arteries were removed 2, 4, 7, 14, 28, or 112 days later for analysis (6 or 13 per time point). Angioplasty dilated arteries by fracturing atheroma and stretching or tearing the media. Cross-sections of injured arteries were analyzed for expression of extracellular matrix components and cell surface integrins that are important in wound healing. Antibodies, riboprobes, or histochemical stains specific for fibrin, hyaluronan, versican (chondroitin sulfate-containing proteoglycan), procollagen-I, elastin, and the alpha 2 beta 1 and alpha V beta 3 integrins were used.. A thin mural thrombus was seen at sites of denudation and plaque fracture (days 2 to 7). This provisional matrix was invaded by leukocytes (days 2 to 4) and alpha-actin-positive smooth muscle cells (SMCs; days 4 to 7). Thrombus was replaced by SMCs expressing hyaluronan and the associated versican proteoglycans (day 14). Versican was expressed throughout the neointima as it enlarged (day 28), but expression later subsided (day 112). Procollagen-I expression initially increased in the adventitia (day 4) and then in the forming neointima (day 14). Procollagen-I expression was found to persist within the adventitia and in the neointima in SMCs nearest the lumen (days 28 to 112). Elastin staining was prominent within the mature neointima (day 112) but not at earlier time points. Integrin expression also increased within the injured artery wall. alpha v beta 3 staining (fibrin[ogen] receptor) increased in the injured media (days 2 to 7) and was then seen throughout the early neointima (day 7). Low level expression of alpha V beta 3 subsequently persisted within the forming neointima (day 28). alpha 2 beta 1 (collagen receptor) expression increased in the neointima in SMCs nearest the lumen (day 28).. Lumen narrowing after angioplasty in this model of atherosclerosis is caused largely by decreased artery wall diameter. The pattern of matrix and integrin expression within the injured artery wall is in many ways analogous to that of healing wounds. These observations suggest that tissue contraction may play a role in lumen narrowing at sites of arterial reconstruction. Strategies to inhibit wound contraction may prove effective in preventing restenosis.

Topics: Angioplasty, Balloon; Animals; Arteriosclerosis; Chondroitin Sulfate Proteoglycans; Elastin; Extracellular Matrix Proteins; Female; Hyaluronic Acid; Iliac Artery; Immunohistochemistry; In Situ Hybridization; Integrins; Lectins, C-Type; Macaca fascicularis; Procollagen; Thrombosis; Tunica Intima; Versicans; Wound Healing

An immunohistochemical analysis was performed to clarify the healing process in implanted vascular grafts in human. Eight woven Dacron grafts and 6 expanded polytetrafluoroethylene grafts were obtained following redo surgery, limb amputation, and autopsy. The implantation periods ranged from 5 days to 148 months. The antibodies used for the analysis were specific to alpha-actin (smooth muscle cells), macrophages, von Willebrand factor (endothelial cells), fibrin, elastin, collagen types 1-5, CD3 (T cells), and CD20 (B cells). At 5 and 24 days after implantation, thrombi containing red blood cells and fibrin covered the anastomotic lines and some of the luminal surfaces of the grafts. Macrophages were scattered throughout the thrombi. At 11-148 months after implantation, either a single layer of endothelial cells or a thin layer of fibrin covered the anastomotic segments of the grafts, and smooth muscle cells and collagen fiber were seen forming anastomotic intimal hyperplasia (AIH). The AIH in the grafts at 94 and 148 months after implantation was almost the same thickness and length a that in the grafts at 11-36 months after implantation Apart from the anastomotic segments, a connective tissue matrix containing collagen fibers covered the luminal surfaces, and some thrombi were noted. Most of the collagen present was type 3, in addition to some type 1, 4, and 5 collagen. No type 2 collagen was noted. Some elastin was also detected in the AIH but not in the midportion of the grafts. Some macrophages and T cells were noted in the perigraft tissues.

Topics: Actins; Antibody Specificity; Antigens, CD20; Biocompatible Materials; Blood Vessel Prosthesis; CD3 Complex; Collagen; Elastin; Endothelium, Vascular; Fibrin; Graft Rejection; Humans; Immunoenzyme Techniques; Immunohistochemistry; Macrophages; Muscle, Smooth, Vascular; Polyethylene Terephthalates; Polytetrafluoroethylene; Thrombosis; von Willebrand Factor

Although directional atherectomy (DA) reduces the plaque burden, successful revascularization is not associated with a reduced restenosis rate when compared with percutaneous transluminal coronary angioplasty (PTCA). The purpose of this study was to compare and contrast the vascular response to DA-induced and PTCA-induced injury. Six to 8 weeks after induction of atherosclerosis, PTCA (n = 34) was performed in one iliac artery and DA in the other (n = 30). Arteries were obtained at 6 time points: 1, 3, 5, 7, 14, and 28 days. Eleven arteries that did not undergo an intervention acted as controls. Radiograms obtained before and after intervention and at euthanization were compared. Morphometric, histologic, and immunohistochemical analyses were performed. Both PTCA and DA resulted in an immediate increase in luminal diameter that subsequently decreased over the ensuing month. PTCA caused deep dissection (7 of 8 arteries), often extending to the adventitia, whereas stand alone DA resulted in deep cleft formation (4 of 5). Of the 30 arteries that underwent DA, 4 exhibited an increase in luminal diameter in the absence of tissue retrieval. Thrombus was observed in both the dissection planes and the clefts within the first 7 days, and cellular ingrowth was appreciated at 5 to 7 days. By 7 days the artery was repaired, and the histologic appearance of the arteries that had undergone PTCA could not be differentiated from the arteries that had undergone DA. Increased intimal and medial collagen and elastin was noted at 14 and 28 days. An increase in the area bordered by the external elastic lamina was observed in both groups. Although successful DA results in tissue removal and the production of a deep tissue cleft and PTCA causes a dissection, both produce a condition in which the arterial injury exposes the arterial media to blood, causing thrombus formation and inflammation with subsequent cellular accumulation into the thrombotic framework.

Topics: Angioplasty, Balloon; Angioplasty, Balloon, Coronary; Animals; Aortic Dissection; Arteriosclerosis; Arteritis; Atherectomy; Atherectomy, Coronary; Collagen; Elastic Tissue; Elastin; Iliac Aneurysm; Iliac Artery; Immunohistochemistry; Rabbits; Radiography; Recurrence; Thrombosis; Tunica Intima; Tunica Media; Wound Healing

To test the hypothesis that atherosclerosis may be initiated by hypoperfusion or thrombotic occlusion of the adventitial vasa vasonum.. In a new model of atherogenesis, an early atherosclerotic lesion may be initiated by removal of the adventitia from the carotid artery of the New Zealand White rabbit, wherein lie the vasa vasorum.. Animal laboratory, University Department of Surgery and Medicine.. Immunocytochemistry was undertaken to demonstrate the presence of smooth muscle cells and macrophages within the intimal lesions. Smooth muscle cells were labelled with a monoclonal antibody designated HHF35 and macrophages were labelled with a rabbit specific, macrophage specific antibody, RAM11. CHIEF RESULTS: In rabbits fed a normal diet, at day 14, the intimal lesion was composed exclusively of smooth muscle cells. By day 28, such lesions had regressed. In rabbits fed a high cholesterol diet, at day 14, the intimal lesion was composed of a mixture of macrophages and smooth muscle cells. By day 42, the pattern of cellular distribution was such that macrophages (present as foam cells) were predominant. In the presence of persistent hypercholesterolaemia these lesions did not regress.. This new model can produce two different cellular responses that may mimic the intimal lesions seen with re-stenosis after angioplasty or in hypercholesterolaemic man and as such, might be useful in separating out these two different pathophysiologies.

Topics: Animals; Arteriosclerosis; Carotid Arteries; Carotid Artery Diseases; Collagen; Elastic Tissue; Elastin; Endothelium, Vascular; Foam Cells; Hypercholesterolemia; Immunohistochemistry; Ischemia; Macrophages; Male; Microscopy, Electron; Muscle, Smooth, Vascular; Rabbits; Thrombosis; Tunica Intima

Chronic rejection of arterial allografts and xenografts results in arterial wall dilation and rupture, making them unsuitable for long-term arterial replacement in vascular surgery. In the arterial wall, as in other organs, the cells probably carry major antigenic determinants. Arterial wall cellular components can be removed by detergent treatment to produce a graftable matrix tube.. We compared the patency and macroscopic and microscopic morphologic changes that occurred in sodium dodecyl sulfate (SDS)-treated and untreated arterial isografts, allografts, and xenografts 2 months after implantation in rats. We quantified elastin, collagen, and nuclear density in the three layers of the graft wall (intima, media, and adventitia) by morphometric methods. The SDS treatment removed endothelial and smooth muscle cells and cells in the adventitia but preserved elastin and collagen extracellular matrix.. All arterial xenografts, whether SDS treated or untreated, were aneurysmal 2 months after grafting, with loss of the medial cellular and extracellular components. In allografts, SDS treatment prevented dilation, reduced adventitial inflammatory infiltration, and preserved medial elastin. The SDS-treated allografts had an evenly distributed, noninflammatory intimal thickening that was richer in elastin fibers than that in untreated allografts.. These results suggest an interspecies, but not an intraspecies, graft antigenicity of arterial extracellular matrix. The SDS treatment prevented chronic rejection of the arterial allograft and led to the proliferation of an elastin-rich and adapted intima.

Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Cell Nucleus; Cell-Free System; Collagen; Detergents; Elastic Tissue; Elastin; Graft Rejection; Guinea Pigs; Male; Rats; Rats, Inbred Lew; Sodium Dodecyl Sulfate; Thrombosis; Tissue Preservation; Transplantation, Heterologous; Transplantation, Homologous; Transplantation, Isogeneic; Tunica Intima; Tunica Media; Vascular Patency

In an experimental study, endothelial cell seeding on glutaraldehyde-fixed and detoxified bioprosthetic tissue, suitable for valve fabrication, was investigated in vitro. These findings were compared to spontaneous endothelial cell ingrowth on vascular grafts fabricated from the same materials. Special consideration was given to the quality of cell attachment with regards to improved shear stress resistance in the endothelial layer covering the bioprosthetic surface. On glutaraldehyde detoxified bovine pericardium, in vitro endothelial cell seeding resulted in uninhibited cell proliferation, but the cells were loosely bound to the underlying tissue. In vivo, endothelial cells grew spontaneously over the surface of vascular implants in direct contact with the bioprosthetic material. In contrast to standard fixed bovine pericardium, a significant decrease in thrombotic appositions could be observed. Cells exhibited intensive production of extracellular matrix, which renders the method of spontaneous in vivo cell ingrowth as the most promising approach for further research.

Topics: Animals; Aorta; Basement Membrane; Bioprosthesis; Cattle; Cell Adhesion; Cell Death; Collagen; Elastin; Endothelium, Vascular; Extracellular Matrix; Glutamates; Glutamic Acid; Glutaral; In Vitro Techniques; Microscopy, Electron; Microscopy, Electron, Scanning; Pericardium; Sheep; Surface Properties; Thrombosis; Tissue Fixation; Tissue Preservation

When human citrated plasma is dialysed against a phosphate buffer containing Ca++, citrate anions are removed, thrombin is generated and soluble fibrinogen derivatives (fibrin monomers and/or soluble fibrin polymers) are formed. These derivatives are able to combine with human or bovine elastin to form a very stable addition product or adduct. The formation of the adduct is dependent on time, Ca++ and thrombin concentrations.

Topics: Animals; Arteriosclerosis; Calcium; Cattle; Citrates; Citric Acid; Dialysis; Elastin; Fibrinogen; Humans; In Vitro Techniques; Solubility; Thrombin; Thrombosis

Two different subendothelial macromolecules have been identified as being thrombogenic: collagen and the microfibrils associated with elastin. The interaction between platelets and collagen involves the binding of platelet membrane receptors by numerous sites repeatedly staggered along a collagen fiber: this explains why the preservation of ordered structures (quaternary and tertiary structures) is so important in the reactivity of collagen towards platelets. In the case of Type III collagen, a nonapeptide has been identified as possibly being part of these repetitive sites. The microfibrils have not yet been characterized, although the biochemical data presently available show that they are acidic glycoproteins resistant to collagenase. Microfibrils extracted from human placenta or bovine aorta induce the aggregation of platelets in a reaction which involves platelet glycoprotein Ib and FVIII/vWF. A general model proposed for explaining platelet adhesion to subendothelium suggests that two different mechanisms should be envisaged depending on the thrombogenic macromolecules (collagen, microfibrils) involved.

Topics: Binding Sites; Blood Vessels; Collagen; Elastin; Endothelium; Factor VIII; Glycoproteins; Humans; Macromolecular Substances; Membrane Proteins; Platelet Adhesiveness; Platelet Aggregation; Platelet Membrane Glycoproteins; Thrombosis; von Willebrand Factor

In a previous paper (1) the organization of an experimental arterial thrombus in rat aorta during the first six days was described. The present paper will set out the thrombus organization during the following weeks and months. Within one month, fibrin and platelets inside the thrombus disappear, and are replaced by smooth muscle cells, collagen and elastin. Elastin was deposited in two forms - granular and strand-like, according to exposure to the pulsatile blood flow. In the course of that period the thrombus surface was covered by endothelial cells. Small, non-endothelialized areas, often with adhering thrombi, were found at all time intervals. The occurrence of thrombi of various ages is suggestive of continuing rethrombosis, presumably due to a permanently disturbed haemodynamical situation.

Topics: Animals; Aorta; Arteriosclerosis; Elastin; Endothelium; Fibrin; Muscle, Smooth, Vascular; Platelet Adhesiveness; Rats; Recurrence; Thrombosis; Time Factors

Partial ligation of the rabbit abdominal aorta with fine silk suture for 48 hours produced a circular band of transmural necrosis. On release of the ligature, blood cells from the lumen and from adventitial vasa vasorum, as well as cells derived by mitosis from the adjacent surviving endothelium and media, participated in the restitution of a continuous endothelial lining and an intact media containing well-differentiated smooth muscle cells within normal medial lamellar units. Initial deposition of a layer of blood platelets on the fibrillar material coating the denuded lumenal surface was followed by ingress from the lumen of polymorphonuclear granulocytes and mononuclear cells. These changes preceded the appearance of mitoses in surviving endothelial and medial smooth muscle cells at the margin of injury. By 24 hours, poorly differentiated cells had accumulated in the central portion of the intima and inner media. Similar cells formed a more extensive, nearly complete lumenal layer which was eventually continuous with and indistinguishable from the adjacent uninjured endothelium. By 7 days, smooth muscle cells repopulated the media, and a collection of less differentiated cells persisted between the restored endothelium and media. By 28 days, the only deviation from normal arterial structure was the persistence at the point of ligature of intimal thickening, consisting of smooth muscle cells and collagen and elastin fibers. Though still present at 6 weeks, this zone became increasingly compact and layered. There was no evidence that fibrin thrombus formation was a consistent feature of the initial reaction or that it played a role in the healing process or in the formation of the intimal lesion. Despite complete circumferential necrosis at the site of ligature, there was no evidence of medial rupture or intramural hemorrhage.

Topics: Animals; Aorta, Abdominal; Blood Platelets; Collagen; Elastin; Endoplasmic Reticulum; Endothelium; Female; Granulocytes; Ligation; Male; Mitosis; Muscle, Smooth; Necrosis; Rabbits; Ribosomes; Thrombosis; Time Factors; Wound Healing

Topics: Amino Acids; Animals; Arteries; Arteriosclerosis; Basement Membrane; Blood Platelets; Collagen; Connective Tissue; Elastin; Extracellular Space; Humans; Hydroxyproline; Iliac Artery; In Vitro Techniques; Microbial Collagenase; Microscopy, Electron; Platelet Adhesiveness; Rabbits; Thrombosis; Trypsin; Umbilical Veins

Topics: Animals; Anticoagulants; Basement Membrane; Blood Flow Velocity; Blood Vessels; Collagen; Connective Tissue; Elastin; Endothelium; Endotoxins; Epithelial Cells; Epithelium; Humans; Microscopy, Electron; Platelet Adhesiveness; Rabbits; Thrombophlebitis; Thrombosis

Topics: Animals; Arteriosclerosis; Basement Membrane; Blood Platelets; Carotid Arteries; Cell Membrane; Cholesterol; Cytoplasm; Elastin; Endoplasmic Reticulum; Endothelium; Femoral Artery; Haplorhini; Hardness; Lipids; Macaca; Male; Microscopy, Electron; Mitochondria; Muscle, Smooth; Pinocytosis; Ribosomes; Staining and Labeling; Sutures; Thrombosis; Time Factors

Topics: Animals; Aorta; Collagen; Elastin; Endothelium; Lipids; Male; Microscopy, Electron; Muscle, Smooth; Rabbits; Thrombosis; Time Factors

Topics: Animals; Dogs; Elastin; Peptide Hydrolases; Perfusion; Thrombosis

Topics: Animals; Basement Membrane; Blood Flow Velocity; Blood Vessels; Collagen; Elastin; Endothelium; Humans; Platelet Adhesiveness; Thrombosis

Topics: Animals; Basement Membrane; Blood Platelets; Blood Vessels; Capillaries; Collagen; Elastin; Fibrinolytic Agents; Hemostasis; Microbial Collagenase; Platelet Adhesiveness; Rabbits; Thrombosis; Trypsin

Topics: Adolescent; Adult; Age Factors; Aged; Aorta; Arteries; Arteriosclerosis; Black People; Calcium; Cerebral Arteries; Cerebrovascular Disorders; Child; Child, Preschool; Cholesterol; Collagen; Coronary Disease; Coronary Vessels; Elastin; Female; Hexosamines; Histocytochemistry; Humans; Infant; Infant, Newborn; Lipids; Male; Middle Aged; Phospholipids; Sex Factors; South Africa; Thrombosis; Triglycerides; White People

Topics: Acute Disease; Animals; Ascitic Fluid; Dogs; Elastic Tissue; Elastin; Enzyme Precursors; Fasting; Female; Hemorrhage; In Vitro Techniques; Male; Pancreatic Elastase; Pancreatic Extracts; Pancreatitis; Thrombosis; Time Factors; Trypsin

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Collagen; Elastin; Factor XII; Hemophilia B; Humans; Kaolin; Rabbits; Thrombosis

Twelve peripheral arteries are described in 59 patients of all ages. Accumulation of ground substance in the media, accompanied by small foci of calcification of the internal elastic lamina, was found in the large leg arteries of young adults, and progressively in a wider series of arteries throughout life. This picture showed no relationship to hypertension, to Mönckeberg's sclerosis, or to the development of atheroma. A notable quantity of ground substance may be a feature of early intimal development, and of a thickened intima in adult life, and probably the major constituent of an organizing thrombus. Organizing thrombi were apparently incidental findings at several sites even in young adults, and showed no association with the state of the arterial wall beneath the lesion, the wall being in fact normal, though accumulated mucopolysaccharide was always present. Atheroma increases with age, and its focal incidence gives way to confluence in the arteries of the leg. Occlusive peripheral artery atheroma was found only in cases where the cause of death was severe atheroma, e.g., coronary artery disease and abdominal aortic aneurysm, or in myxoedema, in which the incidence of occlusive lesions may differ from that in severe generalized atheroma. Elastic tissue is described in all coats of the artery wall, with some variants of the common pattern. The musculo-elastic cushion is not seen after adolescence, and it is suggested that the cushion represents the growing point of the artery. Longitudinal muscle bundles are almost confined to the popliteal artery, where they may form an essential buttress for a large branching artery subject to unusual external stresses. The functions and origin of the ground substance are discussed.

Topics: Adolescent; Adult; Aging; Aorta; Arteries; Arteriosclerosis; Brachial Artery; Carotid Arteries; Child; Elastic Tissue; Elastin; Femoral Artery; Fetus; Fingers; Geriatrics; Growth; Histology; Humans; Hypertension; Infant; Male; Mesenteric Arteries; Microscopy; Pathology; Popliteal Artery; Proteins; Renal Artery; Thrombosis; Tunica Intima; Tunica Media; Vertebral Artery