elastin and Hyperplasia

To present the pathologic analysis of female urethral strictures obtained during reconstructive urethroplasty.. Nine separate female urethral tissue specimens were obtained during dorsal vaginal graft urethroplasty by a single surgeon (S.P.P.). Samples were serially sectioned and fixed in 10% formalin 6 to 12 hours before routine processing in paraffin blocks. Serial 5-µm sections were subjected to H&E, Masson trichrome, and elastin staining. End point analysis included evaluation for epithelial hyperplasia and cell type, mucosal edema, degree of fibroblast/inflammatory cell infiltrate, and elastin fiber density and distribution.. Nine specimens were examined. Six specimens had epithelial linings of stratified squamous epithelium overlying fibrosis (67%), 1 had mixed squamous and urothelial epithelium, and 2 had only urothelial epithelium. Two specimens (29%) showed acute injury with prominent squamous papillary hyperplasia, focal erosion, and patchy mucosal hemorrhage. Areas of urethral stricture were variably thickened, with increased, densely packed collagen fibers and associated mucosal lymphocytic inflammation ranging from mild and patchy to focally dense with lymphoid aggregates. The highest elastin fiber density appeared to be associated with vessels and overlying muscle bundles in the submucosa.. Further elucidation of histopathologic characteristics may illuminate more appropriate therapeutic pathways for female urethral stricture disease management.

Topics: Carcinoma, Squamous Cell; Elastin; Female; Humans; Hyperplasia; Male; Mouth Mucosa; Treatment Outcome; Urethral Stricture; Urothelium

Balloon angioplasty, stent implantation, and application of an arterial clamp during surgery can induce artery injury such as elastin breaks and endothelium injury, but there is little research focused on the injury induced by these therapeutic manipulations. We established a simple and reproducible small animal aortic injury model and examined intramural injection as a potential therapeutic method to alleviate injury.. The abdominal aorta of male Sprague Dawley (SD) rats or C57BL/6 J mice was clamped sequentially throughout its length. Transforming growth factor β1 (TGFβ1), SB431542, lipopolysaccharide (LPS), Necrostatin-1 (Nec-1), rapamycin, or MHY1485 contained in Pluronic gel was injected intramurally at day 0 or day 7. Animals were fed with chow containing 0.25% beta-aminopropionitrile (BAPN) to evaluate the influence of BAPN. All samples were harvested and examined by immunohistochemistry and immunofluorescence.. The clamped rat aorta showed luminal dilation, elastin fiber breaks, neointimal hyperplasia, and dissection (days 0-90). Intramural injection of TGFβ1, rapamycin and Nec-1 showed a protective effect on the injured aorta, whereas SB431542, MHY1485 and LPS showed more severe wall damage. The aortic lumen in rats fed with BAPN was significantly larger than in control rats (day 7). Mouse aorta showed similar injury with neointimal hyperplasia and elastin fiber breaks.. The rodent arterial injury model is reproducible and may mimic early changes of arterial injury. The model accommodates intramural injection of different drugs that may show mechanisms of arterial injury. Although this is a preliminary animal model, the intramural injection method may have potential clinical application in the future.

Topics: Aminopropionitrile; Animals; Aorta, Abdominal; Disease Models, Animal; Elastin; Hyperplasia; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Neointima; Poloxamer; Rats; Rats, Sprague-Dawley; Sirolimus

Airway remodelling, which may include goblet cell hyperplasia / hypertrophy, changes in epithelial integrity, accumulation of extracellular matrix components, smooth muscle hypertrophy and thickening of the lamina reticularis, is a feature of severe asthma and contributes to the clinical phenotype.. Within the U-BIOPRED severe asthma study, we have assessed histological elements of airway remodelling and their relationship to computed tomography (CT) measures of proximal airway dimensions.. Bronchial biopsies were collected from two severe asthma groups, one non-smoker (SAn, n = 28) and one current/ex-smoker (SAs/ex, n = 13), and a mild-moderate asthma group (MMA, n = 28) classified and treated according to GINA guidelines, plus a healthy control group (HC, n = 33). Movat's pentachrome technique was used to identify mucin, elastin and total collagen in these biopsies. The number of goblet cells (mucin+) was counted as a percentage of the total number of epithelial cells and the percentage mucin epithelial area measured. The percentage area of elastic fibres and total collagen within the submucosa was also measured, and the morphology of the elastic fibres classified. Participants in the asthma groups also had a CT scan to assess large airway morphometry.. The submucosal tissue elastin percentage was higher in both severe asthma groups (16.1% SAn, 18.9% SAs/ex) compared with the HC (9.7%) but did not differ between asthma groups. There was a positive relationship between elastin and airway wall area measured by CT (n = 18-20, rho=0.544, p = 0.024), which also related to an increase in elastic fibres with a thickened lamellar morphological appearance. Mucin epithelial area and total collagen were not different between the four groups. Due to small numbers of suitable CT scans, it was not feasible to compare airway morphometry between the asthma groups.. These findings identify a link between extent of elastin deposition and airway wall thickening in severe asthma.

Topics: Adult; Airway Remodeling; Asthma; Biopsy; Bronchi; Bronchoscopy; Case-Control Studies; Collagen; Elastin; Female; Goblet Cells; Humans; Hyperplasia; Male; Middle Aged; Mucins; Tomography, X-Ray Computed

Coronary artery disease (CAD) is the most common cardiovascular disorder. Vascular surgery strategies for coronary revascularization (either percutaneous or open) show a high rate of failure because of restenosis of the vessel, due to phenotypic switch of vascular smooth muscle cells (VSMCs) leading to proliferation and migration. We have previously reported that the inhibition of Kv1.3 channel function with selective blockers represents an effective strategy for the prevention of restenosis in human vessels used for coronary angioplasty procedures. However, delivery systems for controlled release of these drugs have not been investigated. Here we tested the efficacy of several formulations of elastin like recombinamers (ELRs) hydrogels to deliver the Kv1.3 blocker PAP-1 in various restenosis models. The dose and time course of PAP-1 release from ELRs click hydrogels was able to inhibit human VSMC proliferation in vitro as well as remodeling of human vessels in organ culture and restenosis in in vivo models. We conclude that this combination of active compound and advanced delivery method could improve the outcomes of vascular surgery in patients. STATEMENT OF SIGNIFICANCE: Vascular surgery strategies for coronary revascularization show a high rate of failure, because of occlusion (restenosis) of the vessel, due to vascular smooth muscle cells proliferation and migration. We have previously reported that blockers of Kv1.3 channels represent an effective anti-restenosis therapy, but delivery systems for their controlled release have not being explored. Here we tested the efficacy of several formulations of elastin like recombinamers (ELRs) hydrogels to deliver the Kv1.3 blocker PAP-1 in various restenosis models, both in vivo and in vitro, and also in human vessels. We demonstrated that combination of active compound and advanced delivery method could improve the outcomes of vascular surgery in patients.

Topics: Cell Proliferation; Cells, Cultured; Elastin; Humans; Hyperplasia; Muscle, Smooth, Vascular

Current synthetic vascular grafts are not suitable for use in low-diameter applications. Silk fibroin is a promising natural graft material which may be an effective alternative. In this study, we compared two electrospun silk grafts with different manufacturing processes, using either water or hexafluoroisopropanol (HFIP) as solvent. This resulted in markedly different Young's modulus, ultimate tensile strength and burst pressure, with HFIP spun grafts observed to have thicker fibres, and greater stiffness and strength relative to water spun. Assessment in a rat abdominal aorta grafting model showed significantly faster endothelialisation of the HFIP spun graft relative to water spun. Neointimal hyperplasia in the HFIP graft also stabilised significantly earlier, correlated with an earlier SMC phenotype switch from synthetic to contractile, increasing extracellular matrix protein density. An initial examination of the macrophage response showed that HFIP spun conduits promoted an anti-inflammatory M2 phenotype at early timepoints while reducing the pro-inflammatory M1 phenotype relative to water spun grafts. These observations demonstrate the important role of the manufacturing process and physical graft properties in determining the physiological response. Our study is the first to comprehensively study these differences for silk in a long-term rodent model.

Topics: Animals; Aorta, Abdominal; Blood Vessel Prosthesis; Bombyx; Elastic Modulus; Elastin; Fibroins; Hyperplasia; Male; Materials Testing; Microscopy, Electron, Scanning; Neointima; Porosity; Propanols; Prosthesis Design; Rats; Rats, Sprague-Dawley; Solvents; Tensile Strength; Vascular Grafting; Water

Zebrafish (Danio rerio) is widely used as an animal model to understand the pathophysiology of cardiovascular diseases. Here, we present the adult cardiac phenotype of weak atrium, myh6

Topics: Animals; Disease Models, Animal; Elastin; Heart Atria; Hyperplasia; Hypertrophy, Left Ventricular; Hypertrophy, Right Ventricular; Mutation; Myocytes, Cardiac; Myosin Heavy Chains; Zebrafish; Zebrafish Proteins

Topics: Animals; Carotid Arteries; Carotid Artery Injuries; Cathepsins; Cell Movement; Cell Proliferation; Elastin; Hyperplasia; Ligation; Macrophages; Matrix Metalloproteinases; Mice; Mice, Knockout; Myocytes, Smooth Muscle; Neointima; Plaque, Atherosclerotic; Restraint, Physical; RNA, Messenger; Stress, Psychological

Williams syndrome is characterized by obstructive aortopathy attributable to heterozygous loss of. We quantified determinants of luminal stenosis in thoracic aortas of. Deficient circumferential growth is the predominant mechanism for moderate obstructive aortic disease resulting from partial elastin deficiency. Our findings suggest that diverse aortic manifestations in Williams syndrome result from graded elastin content, and SMC hyperplasia causing medial expansion requires additional elastin loss superimposed on

Topics: Adult; Animals; Aorta, Thoracic; Aortic Diseases; Cell Proliferation; Cells, Cultured; Collagen; Constriction, Pathologic; Disease Models, Animal; Elastin; Fibrosis; Genetic Predisposition to Disease; Humans; Hyperplasia; Male; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phenotype; Time Factors; Vascular Stiffness; Vasoconstriction; Williams Syndrome

Maturation failure is the major limitation of arteriovenous fistulas (AVFs) as hemodialysis access conduits. Indeed, 30-50% of AVFs fail to mature due to intimal hyperplasia and insufficient outward remodeling. Elastin has emerged as an important determinant of vascular remodeling. Here the role of elastin in AVF remodeling in elastin haplodeficient (eln(+/-)) mice undergoing AVF surgery has been studied.. Unilateral AVFs between the branch of the jugular vein and carotid artery in an end to side manner were created in wild-type (WT) C57BL/6 (n = 11) and in eln(+/-) mice (n = 9). Animals were killed at day 21 and the AVFs were analyzed histologically and at an mRNA level using real-time quantitative polymerase chain reaction.. Before AVF surgery, a marked reduction in elastin density in the internal elastic lamina (IEL) of eln(+/-) mice was observed. AVF surgery resulted in fragmentation of the venous internal elastic lamina in both groups while the expression of the tropoelastin mRNA was 53% lower in the eln(+/-) mice than in WT mice (p < .001). At 21 days after AVF surgery, the circumference of the venous outflow tract of the AVF was 21% larger in the eln(+/-) mice than in the WT mice (p = .037), indicating enhanced outward remodeling in the eln(+/-) mice. No significant difference in intimal hyperplasia was observed. The venous lumen of the AVF in the eln(+/-) mice was 53% larger than in the WT mice, although this difference was not statistically significant (eln(+/-), 350,116 ± 45,073 μm(2); WT, 229,405 ± 40,453 μm(2); p = .064).. In a murine model, elastin has an important role in vascular remodeling following AVF creation, in which a lower amount of elastin results in enhanced outward remodeling. Interventions targeting elastin degradation might be a viable option in order to improve AVF maturation.

Topics: Animals; Arteriovenous Fistula; Arteriovenous Shunt, Surgical; Carotid Artery, Common; Elastin; Hyperplasia; Jugular Veins; Male; Mice, Inbred C57BL; Vascular Patency; Vascular Remodeling

Infants born with intrauterine growth retardation (IUGR) are at increased risk of adverse pulmonary outcomes at birth, including meconium aspiration and persistent pulmonary hypertension. Preterm infants with IUGR are at especially high risk of developing bronchopulmonary dysplasia (BPD), a disease hallmarked by alveolar hypoplasia. Although vitamin A supplementation has been shown to decrease the incidence of BPD or death in preterm very low birth weight infants, its potential to reduce BPD or death in preterm infants with IUGR remains unknown. We used a well-characterized rat model of caloric restriction to mimic IUGR and determine the impact of IUGR on lung development. We hypothesized that retinoic acid treatment would preserve alveolar formation through increases in key signaling molecules of the retinoic acid signaling pathway. Our results showed that alveolar hypoplasia caused by caloric restriction can be reversed with refeeding, and that retinoic acid prevents the alveolar hypoplasia coincident with the increased expression of elastin and retinoic acid receptor-α and decreased transforming growth factor-β activity in developing rat lungs. These findings suggest that alveolar hypoplasia attributable to caloric restriction is reversible, and raises the possibility that retinoic acid therapy may prove a useful strategy to prevent adverse pulmonary sequelae such as BPD in preterm infants with IUGR.

Topics: Animals; Caloric Restriction; Elastin; Female; Hyperplasia; Lung; Maternal Exposure; Pregnancy; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Signal Transduction; Transforming Growth Factor beta; Tretinoin

To validate the hypothesis that the toxic heavy metal lead (Pb) may be linked to cardiovascular diseases via the initiation of atherosclerosis, in vivo and in vitro studies were conducted.. During the human study part of this project, serum Pb levels of healthy young women were correlated to carotid intima-media thickness. Multivariate logistic regression analyses showed that increased serum Pb levels were significantly associated with an increased intima-media thickness (P=0.01; odds ratio per SD unit, 1.6 [95% CI, 1.1 to 2.4]). In vitro, Pb induced an increase in interleukin 8 production and secretion by vascular endothelial cells. Nuclear factor erythroid 2-related factor-2 is the crucial transcription factor involved in Pb-induced upregulation of interleukin 8. Endothelial cell-secreted interleukin 8 triggered intimal invasion of smooth muscle cells and enhanced intimal thickening in an arterial organ culture model. This phenomenon was further enhanced by Pb-increased elastin synthesis of smooth muscle cells.. Our data support the hypothesis that Pb is a novel, independent, and significant risk factor for intimal hyperplasia.

Topics: Adolescent; Carotid Artery Diseases; Cell Movement; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Elastin; Endothelial Cells; Female; Heat-Shock Proteins; Humans; Hyperplasia; Interleukin-8; Lead; Logistic Models; Mammary Arteries; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NF-E2-Related Factor 2; Odds Ratio; Organ Culture Techniques; Radial Artery; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Tunica Intima; Ultrasonography; Up-Regulation; Young Adult

While the role of hemodynamic variables on the development of intimal hyperplasia in arteriovenous fistulas for hemodialysis has been examined, less is known about the intramural biomechanical factors. In this study, arteriovenous fistulas were created by implantation of e-PTFE grafts between carotid artery and jugular vein in healthy pigs. In vivo recordings exhibited a three-fold pressure and flow elevation in grafted veins after fistula creation, remaining so until sacrifice. The chief morphological observation in grafted vessels was wall thickening at two weeks, serving to restore intramural stresses to homeostatic levels, and a less marked internal diameter enlargement, gradually normalizing intimal shear after four weeks. The residual strains and opening angle, specifying the zero-stress configuration, increased with differences reaching significance at twelve weeks. Association with histomorphological findings on intima, media and adventitia growth disclosed a correlation between intimal hyperplasia and opening angle increase. Elastin and cellular contents diminished opposite to collagen content, most differences occurring within the first four weeks after grafting. Inflation/extension testing showed that post-fistula the vein wall became progressively thicker and stiffer, lacking restoration of compliance to baseline levels. The present data may further our understanding of the dynamics of venous biomechanical remodeling under pressure and flow-overload conditions.

Topics: Animals; Arteriovenous Shunt, Surgical; Carotid Arteries; Collagen; Elastin; Fistula; Hyperplasia; Jugular Veins; Pressure; Renal Dialysis; Shear Strength; Swine; Time Factors

Maintaining arterial duct patency by stent implantation may be advantageous in congenital heart disease management algorithms. Rapamycin, an immunosuppressant drug that demonstrates antiproliferative properties and inhibits smooth muscle cell migration, may deter the intimal hyperplasia that occurs during spontaneous closure and after-stent implantation of the arterial duct.. Twenty-eight Yorkshire piglets (7 to 11 days old; weight, 2.2 to 4.9 kg) underwent stent implantation of the arterial duct (rapamycin-eluting (n=14) or bare metal (n=14) stents, 3.5-mm diameter) and were euthanized at 2, 4, and 6 weeks. Dissected arterial ducts were analyzed for lumen diameter, smooth muscle cell, and extracellular matrix components. Isolated arterial duct-derived smooth muscle cells were cultured in the presence or absence of rapamycin. Cellular proliferation rates were assessed by Ki-67 detection and [(3)H]-thymidine incorporation. No significant neointimal proliferation was present in either stent type at 2 weeks. At 4 weeks, the median luminal diameters of the bare metal stents were 87% (P=0.009), 54% (P=0.004), and 77% (P=0.004) that of the drug-eluting stents at the middle and aortic and pulmonary artery ends, respectively. At 6 weeks, the median luminal diameters of the bare metal stents were 0% (P=0.18), 5% (P=0.25), and 61% (P=0.13) that of the drug-eluting stents at the same respective levels. Complete histological occlusion was found in at least 1 level of the lumen in 9 pigs: 1 (17%) in the BMS group at 4 weeks, 5 (83%) in the BMS group at 6 weeks, and 3 (50%) in the DES group at 6 weeks. In vitro studies demonstrated 50%-lower proliferation rates in rapamycin-treated cultures of duct-derived smooth muscle cell cultures (P<0.001).. Rapamycin has antiproliferative actions on the arterial duct. Drug-eluting stents may be a more efficient tool than current palliative options for maintaining patency in critically duct-dependent states, but there may be a finite time-related benefit.

Topics: Animals; Animals, Newborn; Cell Division; Cells, Cultured; Drug-Eluting Stents; Ductus Arteriosus; Elastin; Heart Defects, Congenital; Hyperplasia; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Sirolimus; Sus scrofa; Tunica Intima; Ultrasonography

Effective application of elastin materials for vascular grafts in tissue engineering requires these materials to retain the elastic and biological properties of native elastin. To clarify the influence of soluble elastin isotypes on vascular smooth muscle cells (VSMCs), soluble elastin was prepared from insoluble elastin by hydrolysis with oxalic acid. Its fractions were separated and classified into three isotypes. Elastin retaining 2.25 mol% of cross-linked structures exhibited significant differentiation of VSMCs, which adhered to the elastin with contraction phenotypes similar to that of native elastin, causing proliferation to cease. This trend was more strongly demonstrated in cotton-like elastin fibers with a new cross-linker. The results suggest that elastin isotypes could be applied as new effective biomaterials for suppressing intimal hyperplasia in vascular grafts.

Topics: Amino Acids; Animals; Bromodeoxyuridine; Cell Differentiation; Chromatography, Gel; Elastin; Flow Cytometry; Hyperplasia; Molecular Structure; Molecular Weight; Muscle, Smooth, Vascular; Spectrophotometry, Ultraviolet; Sus scrofa; Tissue Engineering

A polyclonal antibody to elastin-derived hexapeptide repeat, H-(Val-Gly-Val-Ala-Pro-Gly)(3)-NH(2), was prepared in order to investigate the differences between elastin fibres in intimal hyperplasia and media in human atheroscleroic lesions. The hexapeptide repeat and alpha-elastin were recognized by this polyclonal antibody in enzyme-linked immunosorbent assay (ELISA), but other elastin-derived peptides such as tetrapeptide repeat, pentapeptide repeat and nonapeptide were not. In the series of hexapeptide repeats, H-(VGVAPG)(n)-NH(2) where n is 1-7, the polyclonal antibody reacted strongly with oligomers (n = 3-7) and weakly with dimer (n = 2), but not with monomer (n = 1). CD measurements suggested that the beta-turn structure is important for recognition by the polyclonal antibody. In an immunohistochemical study, elastin was stained more strongly in intimal hyperplasia than in media, suggesting that newly synthesized elastin in intimal hyperplasia is morphologically distinct from that in media.

Topics: Amino Acid Sequence; Antibodies; Atherosclerosis; Circular Dichroism; Dimerization; Elastic Tissue; Elastin; Humans; Hyperplasia; Immunochemistry; Immunohistochemistry; Microscopy; Molecular Sequence Data; Oligopeptides; Tunica Intima

To examine if transforming growth factor-beta3 (TGFbeta3) can attenuate the development of para-anastomotic myointimal hyperplasia in an animal model of small-diameter vascular graft failure.. Under general anesthesia, 10 adult goats underwent bilateral polyurethane interposition graft insertion in the carotid position. Following completion of the anastomoses, each artery received adventitial infiltration of 50 ng of TGFbeta3 around the anastomoses; a placebo was administered to the other side. Postoperatively, each animal received 150 mg of aspirin daily. The arteries were explanted, half at 6 weeks and the remaining 5 at 3 months, for histological examination.. Vessel wall thickness surrounding the anastomosis was reduced by 37% in TGFbeta3-treated arteries compared to placebo at 6 weeks and 3 months, principally due to reduced smooth muscle cell proliferation. There was decreased overall luminal loss on angiography. Total collagen content was not significantly different between TGFbeta3 and placebo sides. Further analysis for the subendothelial matrix component collagen type VIII showed decreased levels on the treated side. Total elastin content was reduced on the TGFbeta3-treated side.. Direct single-dose subadventitial infiltration of TGFbeta3 following insertion of an interposition graft reduces SMC proliferation and elastin content. It would appear that TGFbeta3 holds promise as a prophylaxis against the development of myointimal hyperplasia, the predominant cause of graft failure in peripheral bypass surgery.

Topics: Actins; Anastomosis, Surgical; Animals; Blood Vessel Prosthesis Implantation; Carotid Artery, Common; Cell Proliferation; Collagen Type VIII; Elastin; Female; Goats; Graft Occlusion, Vascular; Hyperplasia; Models, Animal; Muscle, Smooth, Vascular; RNA, Messenger; Transforming Growth Factor beta3; Vascular Patency

Diabetes is an independent risk factor for the development of neointimal hyperplasia and subsequent vein graft failure after coronary or peripheral artery bypass grafting. We evaluate a new mouse model of surgical vein grafting to investigate the mechanisms of neointimal formation in the setting of type 2 diabetes.. Surgical vein grafts were created by inserting vein segments from age-matched C57BL/KsJ wild-type mice into the infra-renal aorta of lepr(db/db) diabetic and C57BL/KsJ wild-type mice. Mice were euthanized &4 weeks later, and vein grafts were analyzed using morphometric and immunohistochemical techniques. A significant increase in neointimal formation was noted in lepr(db/db) mice (139+/-64 versus 109+/-62 mm2; P=0.008) after 4 weeks. This difference was mainly secondary to an increase in collagen formation within the lesion in the vein grafts from lepr(db/db) mice (0.53+/-0.4 versus 0.44+/-0.05; P<0.001), whereas only slight increases (P=not significant) in alpha actin-stained smooth muscle cells were noted in the lepr(db/db) mice.. We established a new physiologically relevant model of surgical vein grafting in mice. In this report, type 2 diabetes was associated with significant increase in extracellular matrix deposition in addition to increased smooth muscle cell deposition. This new model may allow mechanistic studies of cellular and molecular pathways of increased neointimal formation in the setting of diabetes.

Topics: Actins; Animals; Aorta, Abdominal; Bioprosthesis; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Collagen; Diabetes Mellitus, Type 2; Disease Models, Animal; Elastin; Extracellular Matrix; Hyperplasia; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Muscle, Smooth, Vascular; Receptors, Cell Surface; Receptors, Leptin; Transplantation, Heterotopic; Tunica Intima; Vena Cava, Inferior

This study tested the hypotheses that chronic allergic inflammation induces not only bronchial but also lung parenchyma remodeling, and that these histologic changes are associated with concurrent changes in respiratory mechanics. For this purpose, airway and lung parenchyma remodeling were evaluated by quantitative analysis of collagen and elastin, immunohistochemistry (smooth-muscle actin expression, eosinophil, and dendritic cell densities), and electron microscopy. In vivo (airway resistance, viscoelastic pressure, and static elastance) and in vitro (tissue elastance, resistance, and hysteresivity) respiratory mechanics were also analyzed. BALB/c mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. A marked eosinophilic infiltration was seen in lung parenchyma and in large and distal airways. Neutrophils, lymphocytes, and dendritic cells also infiltrated the lungs. There was subepithelial fibrosis, myocyte hypertrophy and hyperplasia, elastic fiber fragmentation, and increased numbers of myofibroblasts in airways and lung parenchyma. Collagen fiber content was increased in the alveolar walls. The volume proportion of smooth muscle-specific actin was augmented in distal airways and alveolar duct walls. Airway resistance, viscoelastic pressure, static elastance, and tissue elastance and resistance were significantly increased. In conclusion, prolonged allergen exposure induced remodeling not only of the airway wall but also of the lung parenchyma, leading to in vivo and in vitro mechanical changes.

Topics: Actins; Airway Resistance; Animals; Asthma; Bronchi; Collagen; Disease Models, Animal; Elastin; Hyperplasia; Hypertrophy; In Vitro Techniques; Lung; Mice; Mice, Inbred BALB C; Microscopy, Electron; Muscle, Smooth; Pulmonary Alveoli; Pulmonary Eosinophilia; Pulmonary Fibrosis; Respiratory Hypersensitivity; Respiratory Mechanics

The patency of arteriovenous (AV) polytetrafluoroethylene grafts for hemodialysis is impaired by intimal hyperplasia (IH) at the venous outflow tract. IH mainly consists of vascular smooth muscle cells, fibroblasts, and extracellular matrix proteins. Because matrix metalloproteinases (MMPs) are enzymes able to degrade extracellular matrix proteins such as elastin and collagen and also stimulate migration of vascular smooth muscle cells, we hypothesized that BB2983 (a broad-spectrum MMP inhibitor) could reduce IH in AV grafts.. In 12 pigs, AV grafts were created bilaterally between the carotid artery and the jugular vein. Six pigs received the oral MMP inhibitor (MMPi), and six pigs served as a control. Four weeks after AV shunting, the grafts and adjacent vessels were excised and underwent histologic analysis. Quantification of elastin content was performed on Elastin von Gieson-stained sections.. At the venous outflow tract, IH was strongly inhibited after MMPi when compared with the control group (1.02 +/- 0.26 mm(2) vs 2.14 +/- 0.38 mm(2); P =.027). The medial area did not differ significantly. In the control group elastin density decreased compared with nonoperated veins. This decrease was not observed in the MMPi group (nonoperated, 6.3% +/- 0.4%; MMPi, 7.2% +/- 0.7% vs untreated, 3.6% +/- 0.5%; P =.0004). Outward remodeling of the vein was not influenced by MMP inhibition.. MMPi reduces IH formation at the venous outflow tract of AV grafts in pigs, probably by inhibiting elastin degradation. These data suggest that MMP inhibitors might be useful for minimizing IH in AV grafts, thus prolonging patency rates of AV grafts in patients on hemodialysis.

Topics: Animals; Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis; Carotid Arteries; Elastin; Female; Graft Occlusion, Vascular; Hyperplasia; Jugular Veins; Matrix Metalloproteinase Inhibitors; Polytetrafluoroethylene; Renal Dialysis; Swine; Tunica Intima; Vascular Patency

Seminal to the process of arterial restenosis after balloon angioplasty is extracellular matrix degradation by metalloproteinases (MMPs); activity of these proteins is strongly inhibited by the tissue inhibitors of MMPs (TIMPs). Here we exploit gene transfer using an adeno-associated virus (AAV) for TIMP1 gene delivery in a rat model of intimal hyperplasia. High-titer AAV-Timp1 efficiently transduced human coronary artery smooth muscle cells (SMCs) in vitro and inhibited the capacity of these cells to migrate through a Matrigel barrier. In injured rat carotid arteries, AAV vectors were found to transduce SMCs efficiently and to maintain transgene expression for several weeks in vivo. In AAV-Timp1-transduced animals, the intima:media ratio of injured carotids was significantly reduced by 70.5% after 2 weeks, by 58.5% after 1 month, and by 52.4% after 2 months from treatment. The decrease in intimal hyperplasia was paralleled by a significant inhibition of collagen accumulation and by increased elastin deposition in the neointima, two findings that relate to the inhibition of MMP activity. These results indicate that AAV vectors are efficient tools for delivering genes to the arterial wall and emphasize the importance of MMPs for the generation of intimal hyperplasia. Local TIMP1 gene transfer might thus represent an efficient strategy to prevent restenosis.

Topics: Angioplasty, Balloon; Animals; Arterial Occlusive Diseases; Carotid Arteries; Collagen; Dependovirus; Elastin; Genetic Therapy; Genetic Vectors; Humans; Hyperplasia; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Muscle, Smooth, Vascular; Rats; Tissue Inhibitor of Metalloproteinase-1; Transfection; Tunica Intima

The loss of patency constitutes the major complication of arteriovenous (AV) polytetrafluoroethylene hemodialysis grafts. In most cases, this graft failure is due to intimal hyperplasia at the venous outflow tract, including proliferation of vascular, smooth muscle cells and fibroblasts with deposition of extracellular matrix proteins. Thus far, procedures developed for improving patency have proven unsuccessful, which can be partly explained by the lack of relevant animal models. For this purpose, we developed a porcine model for AV graft failure that will allow the assessment of promising therapeutic strategies in the near future.. In 14 pigs, AV grafts were created bilaterally between the carotid artery and the jugular vein using expanded polytetrafluoroethylene. Two, 4 or 8 weeks after AV shunting, the grafts and adjacent vessels were excised and underwent histologic analysis.. From 2 weeks onwards, a thick neo-intima developed at the venous anastomosis, predominantly consisting of alpha-actin-positive vascular smooth muscle cells (VSMC). Intimal area increased over time, coinciding with a decreased graft flow. Grafts remained patent for at least 4 weeks. At 8 weeks, patency rates declined to less than 50% due to thrombus formation superimposed on progressive neo-intima formation.. Implantation of an AV graft between the carotid artery and jugular vein in pigs causes a rapid neo-intimal response, accompanied by a loss of patency of 50% at 8 weeks after surgery. This model offers a suitable tool to study local interventions aimed at the improvement of AV graft patency rates.

Topics: Animals; Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis; Carotid Arteries; Collagen; Elastin; Female; Graft Occlusion, Vascular; Hyperplasia; Models, Animal; Models, Cardiovascular; Platelet Aggregation Inhibitors; Polytetrafluoroethylene; Swine; Treatment Failure; Tunica Intima

To quantitate the pathologic features of carcinoid plaques in a relatively large number of surgical specimens from a single institution.. Medical records, operative reports, and surgical specimens were reviewed from all patients with carcinoid heart disease who underwent cardiac valvular surgery at Mayo Clinic, Rochester, Minn, between 1980 and 2000.. The study group included 75 patients (45 men, 30 women) who ranged in age from 26 to 78 years (mean, 59 years). From these 75 patients, 139 valves had been excised surgically (73 tricuspid, 55 pulmonary, 6 mitral, 5 aortic). Pure regurgitation was the most common dysfunctional state of the tricuspid valve (80% [60/75]), mitral valve (97% [32/33]), and aortic valve (96% [23/24]). The pulmonary valve was more often both stenotic and insufficient (52% [37/71]) than purely regurgitant (30% [21/71]). In all cases, valve dysfunction was attributed to the presence of carcinoid plaques, which caused both thickening and retraction. Thickening was the result of both cellular proliferation and deposition of extracellular matrix. Proliferation of myofibroblasts was observed in all plaques and was mild in 49% (68/139) and moderate or severe in 51% (71/139). Extracellular matrix included collagen (in 99% of the 139 valves), myxoid ground substance (98% [136/139]), and elastin (20% [28/139]). Carcinoid plaques were also involved by neovascularization (94% [131/139]), chronic inflammation (94% [131/139]), and mast cell infiltration (64% [89/139]). Severe thickening was attributable primarily to collagen deposition in tricuspid valves and to myofibroblast proliferation and myxoid matrix in pulmonary valves.. Among patients undergoing valvular surgery for carcinoid heart disease, tricuspid and pulmonary valves represented 92% of the excised valves (128/ 139). Although numerous cellular and extracellular features were common to the carcinoid plaques, variability in their relative expression produced appreciable differences in the histologic appearance among the plaques.

Topics: Adult; Aged; Aortic Valve Insufficiency; Carcinoid Heart Disease; Collagen; Elastin; Female; Fibroblasts; Hemodynamics; Humans; Hyperplasia; Inflammation; Male; Mast Cells; Middle Aged; Mitral Valve Insufficiency; Neovascularization, Pathologic; Pulmonary Valve Insufficiency; Retrospective Studies; Severity of Illness Index; Tricuspid Valve Insufficiency

Intimal hyperplasia is one of the main responses of the vascular wall to injury. In the current study, we tested the hypothesis that endoluminal seeding of host syngeneic vascular cells could limit intimal hyperplasia induced by either mechanical deendothelialization or chronic allograft rejection in rat aorta.. An experimental model of in situ seeding of syngeneic endothelial cells, smooth muscle cells (SMCs), and fibroblasts (FIBs) was used in mechanically deendothelialized and allografted aortas. In a preliminary study, the ability of the three cell types (n = 5 per group) to seed on the deendothelialized luminal surface of the aortic wall was evaluated after 2 days, with the use of fluorescent PKH as marker. In the first model, the abdominal aorta of Lewis rats was deendothelialized (n = 6) or deendothelialized and seeded with either SMCs (n = 6) or FIBs (n = 6) before flow was restored. In the allograft model, aortas were harvested from dark agouti rats and orthotopically grafted in Lewis receivers, directly (n = 6) or after deendothelialization. Deendothelialization was performed alone (n = 6) or associated with the seeding of similar host (Lewis) syngeneic SMCs (n = 6) or FIBs (n = 6). Results were evaluated at 2 months with histologic and morphometric methods.. SMCs and FIBs were able to adhere in situ to the deendothelialized aortic wall, whereas endothelial cells were not. In mechanically deendothelialized aortas, the seeding of syngeneic SMCs led to a significant reduction in intimal thickness compared with deendothelialized aortas or FIB-seeded aortas (26.9 +/- 1.7 microm vs 55.5 +/- 1.7 and 56.7 +/- 1.7 microm, respectively), and a lower nuclear content (382.2 +/- 35.7 microm(2) vs 779.6 +/- 65.9 and 529.6 +/- 24.3 microm(2), respectively) of neointima. After SMC seeding, intimal hyperplasia was richer in elastin, whereas after FIB seeding it was richer in collagen. In allografts, the seeding of syngeneic SMC led to a significant reduction in intimal thickness compared with control aortas, deendothelialized aortas, or FIB-seeded aortas (31.6 +/- 1.1 microm vs 88.55 +/- 2.8, 74.6 +/- 2.9, and 85.7 +/- 2.6 microm, respectively), and a reduced nuclear content of the neointima (444.9 +/- 23.4 microm(2) vs 1529.1 +/- 116, 972.3 +/- 50, and 645.2 +/- 32.4 microm(2), respectively). Differences observed in the extracellular matrix composition were equivalent to those observed in the mechanically deendothelialized model.. Our results suggest that endoluminal seeding of syngeneic SMCs can be effective in reducing intimal hyperplasia both in a deendothelialization model and in arterial allografts. SMC and FIB endoluminal seeding led to a significatively different accumulation of extracellular matrix in the intima.

Topics: Analysis of Variance; Animals; Aorta, Abdominal; Cell Adhesion; Cell Division; Cell Movement; Chronic Disease; Collagen; Disease Models, Animal; Elastin; Fibroblasts; Graft Rejection; Hyperplasia; Inflammation; Male; Muscle, Smooth, Vascular; Rats; Rats, Inbred Lew; Rats, Inbred Strains; Time Factors; Transplantation, Homologous; Transplantation, Isogeneic; Tunica Intima; Wound Healing

Sympathetic hyperactivity is observed in several disease states and may contribute to cardiovascular hypertrophic remodeling. Endothelin has been suggested to be a mediator of hypertrophy.. To examine the involvement of endothelin in maintaining the growth response induced by exogenous norepinephrine.. Rats were treated with norepinephrine (2.5 microg/Kg per min subcutaneously) for 2 and 4 weeks, alone or in association with the selective endothelin-A (ETA) receptor antagonist, darusentan (LU135252, 30 mg/Kg per day orally) for weeks 3 and 4.. Increases in medial cell number and accumulation of collagen and elastin characterized norepinephrine-induced aortic remodeling. These effects occurred without marked changes of mean arterial pressure, but may be related to enhanced pressure variability in addition to direct effects of norepinephrine. Inhibition of ETA receptors by darusentan reversed aortic alterations produced by infusion of norepinephrine. Evaluation of medial apoptosis did not reveal any significant change in any group at 4 weeks.. Antagonism of ETA receptors effectively and rapidly reversed norepinephrine-induced aortic structural and compositional changes, suggesting a central role of endothelin in mediating this response. Thus, ETA receptor antagonists may help to regress large artery remodeling in conditions of increased circulating catecholamine concentrations.

Topics: Animals; Aorta; Apoptosis; Arteries; Cell Count; Collagen; Elastin; Endothelin Receptor Antagonists; Endothelins; Extracellular Matrix; Hemodynamics; Hyperplasia; Male; Muscle, Smooth, Vascular; Norepinephrine; Phenylpropionates; Pyrimidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A

This study was conducted to assess the net proteolytic activity of human non-Hodgkin's lymphomas (NHLs). We have compared the extracellular matrix (ECM)-degradative abilities of human NHLs, reactive lymphoid hyperplasias, and established lymphoid cell lines using Matrigel invasion and elastin degradation assays. The inhibition studies allowed identification of the classes of proteinases involved in ECM degradation. Our results indicate that lymphocytes and other leukocytes derived from both human NHLs and reactive lymphoid hyperplasias are capable of Matrigel penetration, but only cells derived from the high-grade human NHLs degrade elastin in vitro. Established lymphoid cell lines (both malignant and Epstein-Barr virus immortalized) do not produce MMP-9, do not penetrate the Matrigel, and do not degrade elastin. Moreover, in human NHLs, elastolytic activity is blocked by metalloproteinase inhibitors, while inhibitors of the other classes of proteolytic enzymes have only minor effects. This study identifies metalloproteinases as the most important class of proteinases involved in ECM degradation by NHLs. The previous studies suggest that, within this class, MMP-9 represents the key enzyme that plays a role in the biological aggressiveness of human NHLs.

Topics: Cell Line; Collagen; Collagenases; Drug Combinations; Elastin; Enzyme Inhibitors; Extracellular Matrix; Humans; Hyperplasia; Laminin; Lymphoid Tissue; Lymphoma, Non-Hodgkin; Matrix Metalloproteinase 9; Metalloendopeptidases; Neoplasm Invasiveness; Peptide Hydrolases; Proteoglycans

The thrombospondins are a family of extracellular calcium-binding proteins that modulate cellular phenotype. Thrombospondin-1 (TSP-1) reportedly regulates cellular attachment, proliferation, migration, and differentiation in vitro. To explore its function in vivo, we have disrupted the TSP-1 gene by homologous recombination in the mouse genome. Platelets from these mice are completely deficient in TSP-1 protein; however, thrombin-induced platelet aggregation is not diminished. TSP-1-deficient mice display a mild and variable lordotic curvature of the spine that is apparent from birth. These mice also display an increase in the number of circulating white blood cells, with monocytes and eosinophils having the largest percent increases. The brain, heart, kidney, spleen, stomach, intestines, aorta, and liver of TSP-1-deficient mice showed no major abnormalities. However, consistent with high levels of expression of TSP-1 in lung, we observe abnormalities in the lungs of mice that lack the protein. Although normal at birth, histopathological analysis of lungs from 4-wk-old TSP-1-deficient mice reveals extensive acute and organizing pneumonia, with neutrophils and macrophages. The macrophages stain for hemosiderin, indicating that diffuse alveolar hemorrhage is occurring. At later times, the number of neutrophils decreases and a striking increase in the number of hemosiderin-containing macrophages is observed associated with multiple-lineage epithelial hyperplasia and the deposition of collagen and elastin. A thickening and ruffling of the epithelium of the airways results from increasing cell proliferation in TSP-1-deficient mice. These results indicate that TSP-1 is involved in normal lung homeostasis.

Topics: Animals; Blood Platelets; Cells, Cultured; Collagen; Congenital Abnormalities; DNA; Elastin; Eosinophils; Epithelial Cells; Genetic Vectors; Hemorrhage; Hemosiderin; Homeostasis; Hyperplasia; Leukocyte Count; Lordosis; Lung; Macrophages; Mice; Mice, Knockout; Monocytes; Neutrophils; Platelet Aggregation; Pneumonia; Proteins; Radiography; Recombination, Genetic; Restriction Mapping; Ribonucleases; Thrombin; Thrombospondin 1; Transfection

The arterial wall injury associated with arterial graft implantation causes smooth muscle cells (SMCs) in the media to migrate and proliferate in the intima at the graft-artery junction resulting in anastomotic intimal hyperplasia (AIH). An important step in developing a small-diameter prosthesis may be to stimulate endothelialization and thereby inhibit AIH. In this study, we investigated the effect of coacervated and crosslinked alpha-elastin on proliferation of SMCs and endothelial cells (ECs) in vitro. Coacervation is an important step in the conversion of proelastin to make an elastin fiber in vivo. SMCs and ECs were prepared from porcine aortic media and endothelium, respectively. SMCs and ECs (three to five passages, 4 x 10[4] cells/well) were seeded onto 12 well plates, coated and crosslinked with 0 or 10 mg/mL of coacervated alpha-elastin. After the 1st, 2nd, or 3rd day of cultivation, proliferation was assayed by scintillation counting of [3H]-thymidine incorporation. For the 4th day only, 0, 0.1, 1, 10 mg/mL concentration of coacervated alpha-elastin was coated and crosslinked. SMC proliferation (1st, 2nd day: p<0.005; 3rd, 4th day: p<0.0001) was significantly inhibited over time and dose dependently, eg, 0.1 mg/mL (45.7+/-2.3%: % of control p<0.005), 1 mg/mL (5.9+/-0.7%, p<0.0005), 10 mg/mL (2.8+/-0.4%, p<0.0005). EC proliferation was inhibited over time by 10 mg/mL of coacervated alpha-elastin (2nd, 3rd day: p<0.005; 4th day: p<0.0001), but proliferation (132.8+/-9.9%: % of control p=NS) was stimulated by 0.1 mg/mL of coacervated alpha-elastin. These results suggest that coating and crosslinking a coacervated alpha-elastin into the structure of arterial prosthesis may inhibit AIH and stimulate endothelialization.

Topics: Alkanesulfonic Acids; Analysis of Variance; Anastomosis, Surgical; Animals; Aorta; Arteries; Blood Vessel Prosthesis; Buffers; Cell Division; Cell Movement; Cells, Cultured; Chemical Precipitation; Cross-Linking Reagents; Dose-Response Relationship, Drug; Elastin; Endothelium, Vascular; Hyperplasia; Morpholines; Muscle, Smooth, Vascular; Polypropylenes; Prosthesis Design; Protein Precursors; Radiopharmaceuticals; Surface Properties; Swine; Thymidine; Tritium; Tunica Intima; Tunica Media

The theory that "viable" valve grafts have superior durability because the donor cell population of the leaflets survives implantation and functions normally, thus maintaining leaflet integrity, is still not definitively proven. The postulate has been investigated for grafts produced and used at Green Lane Hospital by examining a series of 155 removed at reoperation following up to 21.3 years of implantation.. Leaflet cellularity at explantation was assessed histologically. An additional 55 cases were also assessed by tissue culture. Cell origin for six positive cultures was determined by comparison of DNA of the culture with that of the recipient's blood cells.. Grafts known to be nonviable at implantation lacked leaflet fibroblasts but sometimes showed ongrowth of fibrous tissue derived from the recipient's aorta. Grafts potentially viable at implantation showed three main patterns of fibroblastic growth: (1) relatively sparse, scattered cells; (2) focal hyperplastic growth with intervening acellular tissue that was prone to rupture; and (3) widely disseminated, vigorous growth causing abnormal thickening. The first pattern was associated with recipient cells, and both the second and third patterns were associated with nonrecipient cells.. Donor cells surviving implantation do not maintain a normal leaflet architecture and may lead to failure by producing loss of leaflet flexibility.

Topics: Anti-Bacterial Agents; Aortic Valve; Cell Division; Cell Lineage; Cell Survival; Collagen; Cryopreservation; Culture Techniques; DNA; Drug Therapy, Combination; Elastin; Fibroblasts; Follow-Up Studies; Graft Survival; Humans; Hyperplasia; Middle Aged; Pliability; Proteoglycans; Reoperation; Rupture; Sterilization; Tissue Survival; Transplantation Chimera; Transplantation, Homologous

The cellular basis of adaptations occurring during the development of megacolon was studied with the lethal spotted mouse model. Age-dependent changes in the length-force characteristics of the colon reach a steady state by 3-4 mo and include an increased relative force development at very short muscle lengths. In megacolon the following occur: 1) structural remodeling expressed as a greater increase in the fraction of maximum force production at short lengths, a shift of optimum length (Lo) to longer lengths, and no change in force per square centimeter; 2) hypertrophy and hyperplasia of both circular and longitudinal muscle; 3) high resting compliance consistent with no disproportionate change in collagen or elastin composition; 4) marked distension so that in situ circumference approximately 1.8 Lo, where active force production is low, and 5) slack length approximately 0.65 Lo, as in normal colon. Biochemical remodeling in megacolon includes disproportionate increases in ATP and phosphocreatine concentration, with 3.5-fold more preformed phosphagen than in normal colon. The myosin concentration is the same in both muscles, but the actin concentration is 1.5-fold greater in megacolon. Most of the cellular changes in megacolon would facilitate high active force output from the muscle at much larger intestinal diameters.

Topics: Actins; Adenine Nucleotides; Aging; Animals; Collagen; Colon; Creatine; Creatinine; Elastin; Electric Stimulation; Heterozygote; Hyperplasia; Hypertrophy; In Vitro Techniques; Intestinal Mucosa; Megacolon; Mice; Mice, Mutant Strains; Muscle Contraction; Muscle, Smooth; Myosins; Potassium

The aim of this study was to investigate prospectively the epithelialization process in the healing temporalis myofascial flap (TMF). Eight cats underwent maxillectomy and immediate reconstruction with TMF. They were killed at the determined time and the reconstructed maxillae were processed for examination by light microscopy and scanning electron microscopy. Results revealed that epithelialization of the healing TMF was initiated by hyperplastic changes followed by active migration of epithelial cells deriving from the wound margins. The partial maxillectomy wound was completely covered by a smooth oral mucosa at postoperative week 24. The mucosa had histological and ultrastructural features different from normal palatal mucosa.

Topics: Animals; Cats; Cell Movement; Collagen; Connective Tissue; Edema; Elastin; Epithelium; Fascia; Granulation Tissue; Hyperplasia; Inflammation; Keratins; Lymphocytes; Macrophages; Maxilla; Microscopy, Electron, Scanning; Mouth; Mouth Mucosa; Plasma Cells; Prospective Studies; Regeneration; Surgical Flaps; Temporal Muscle; Wound Healing

To study the cytotoxic effect of photodynamic therapy (PDT) on myointimal hyperplasia (MIH) in 120 New Zealand white rabbits using the chromophore chloroaluminum phthalocyanine tetrasulfonate (APtS).. A common carotid artery (CCA) injury model was used to initiate MIH. Photodynamic therapy was administered 1 week after injury (inhibition arm) or 6 weeks after injury (treatment arm). The inhibition arm CCAs were harvested 6 weeks after therapy. The treatment arm CCAs were harvested 1 week or 6 weeks after therapy. Each evaluation included four subgroups (n = 10 each): control, drug only, laser only, and drug plus laser.. An established CCA balloon injury model was used. Photodynamic therapy was administered by exposing CCAs to continuous external laser irradiation 30 minutes after treatment with a 2.5-mg/kg intravenous dose of APtS (fluence = 25 J/cm2, lambda = 672 nm). The control and drug-only subgroups received sham reoperations without laser exposure.. Following harvest, the CCAs were evaluated for area of stenosis and cell density.. In the inhibition arm, no PDT effect was seen on intimal cell density or area stenosis. In the treatment arm, intimal cell density was markedly diminished (P < .05) in the rabbits in the drug-laser group that were killed 1 week but not 6 weeks after PDT compared with rabbits in the control, drug-only, and laser-only groups. Area stenosis was not significantly affected by PDT.. Marked acute cytotoxicity of PDT on MIH was verified in vivo in the treatment arm. No sustained benefit of PDT was seen in the inhibition or the treatment arms. Refinements in dosimetry will be necessary to achieve long-term benefit of PDT for MIH.

Topics: Animals; Carotid Artery Injuries; Carotid Artery, Common; Collagen; Elastin; Hyperplasia; Indoles; Microscopy, Electron; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Rabbits; Tunica Intima

Topics: Diagnosis, Differential; Elastin; Female; Fibroma; Humans; Hyperplasia; Male; Middle Aged

Elastin synthesized in response to vascular injury was characterized in terms of its amino acid composition, the biosynthetic labeling of the desmosines and of the heat coacervable polypeptides present in the 2 M urea extract. Neointimal hyperplasia of the chronic variety was induced in rabbit aorta by superficial mechanical lesions. At 4 months following injury the reendothelialized neointimal thickening and the media were excised. Aliquot samples were incubated with [3H] lysine, extracted with 2 M urea, 0.1 M Tris, pH 7.4 and hydrolysed with collagenase. In the residue of the digests the [3H] desmosines were quantified after electrophoretic separation. Elastin was purified from the nonlabeled aliquots of the media and neointimal hyperplasia. It accounted for 60% and 25% of the dry weight of the media and the neointima respectively. Elastin isolated from the media and the neointima had essentially the same amino acid composition. The incorporation of [3H] lysine into desmosines and into coacervable polypeptides indicated that the synthesis of crosslinked elastin is still active in the hyperplasia at 4 months following injury.

Topics: Amino Acids; Animals; Aorta; Elastin; Hyperplasia; Rabbits

Quantitative levels of mRNAs coding for elastin, types I and III procollagen and gamma-actin were measured in porcine vascular material following balloon catheterization. A balloon catheter was introduced into the thoracic aorta and jugular vein of 3-6 week old pigs; following distention and six days of postoperative recovery, tissue samples were obtained for histopathology, electron microscopy, RNA extraction and mRNA quantitation. Using a series of mammalian cDNA clones and the procedure of slot blot hybridization, we have shown that elastin and types I and III procollagen mRNA levels rose significantly during the postoperative period following vascular distention. The increase correlated with an increase in the cell mass present in both the venous and arterial intimal layers. Changes in gamma-actin mRNA levels were also associated with this rapid proliferative response but in arterial tissue only.

Topics: Actins; Animals; Blotting, Northern; DNA; Elastin; Endothelium, Vascular; Hyperplasia; Procollagen; RNA, Messenger; Stress, Mechanical; Swine

Vascular structural changes were studied during the development of two-kidney one-clip renal hypertension. The weight of the arteries and the concentration and total amount of ribonucleic acid, deoxyribonucleic acid, alkali-soluble proteins, collagen and elastin of the vascular wall were measured. Tritiated thymidine uptake was also determined 15 and 30 days after clipping. Hypertension developed in 58% of the animals while the rest remained normotensive. A significant increase in artery weight and in the total amount of nucleic acids and proteins was found in hypertensive rats. The uptake of 3H thymidine by the arteries of hypertensive rats was significantly increased 15 days after clipping. This increment showed a significant correlation with blood pressure levels. Present data seem to indicate that the increase in vessel wall dimensions observed is partly due to an increase in the number of smooth muscle cells during the acute phase; this alteration appears to be mainly due to the rise in blood pressure.

Topics: Animals; Blood Pressure; Cardiomegaly; Collagen; Disease Models, Animal; DNA; Elastin; Hyperplasia; Hypertension, Renal; Hypertension, Renovascular; Male; Muscle, Smooth, Vascular; Myocardium; Rats; Rats, Inbred Strains; RNA; Thymidine

Topics: Air Pollution; Animals; Autoradiography; Collagen; Elastin; Female; Hyperplasia; Lung; Lung Diseases; Male; Mice; Microscopy, Electron; Organ Size; Oxygen Consumption; Pulmonary Alveoli; Smog

Topics: Animals; Blood Protein Electrophoresis; Elastin; Extremities; Fibroblasts; Hyperplasia; Injections, Intraperitoneal; Lymph Nodes; Macrophages; Phagocytosis; Rats