elastin and Rupture--Spontaneous

There is a need for animal models of plaque rupture. We previously reported that elastin fragmentation, due to a mutation (C1039G(+/-)) in the fibrillin-1 (Fbn1) gene, promotes atherogenesis and a highly unstable plaque phenotype in apolipoprotein E deficient (ApoE(-/-)) mice on a Western-type diet (WD). Here, we investigated whether plaque rupture occurred in ApoE(-/-)Fbn1(C1039G+/-) mice and was associated with myocardial infarction, stroke, and sudden death.. Female ApoE(-/-)Fbn1(C1039G+/-) and ApoE(-/-) mice were fed a WD for up to 35 weeks. Compared to ApoE(-/-) mice, plaques of ApoE(-/-)Fbn1(C1039G+/-) mice showed a threefold increase in necrotic core size, augmented T-cell infiltration, a decreased collagen I content (70 ± 10%), extensive neovascularization, intraplaque haemorrhage, and a significant increase in matrix metalloproteinase-2, -9, -12, and -13 expression or activity. Plaque rupture was observed in 70% of ascending aortas and in 50% of brachiocephalic arteries of ApoE(-/-)Fbn1(C1039G+/-) mice. In ApoE(-/-) mice, plaque rupture was not seen in ascending aortas and only in 10% of brachiocephalic arteries. Seventy percent of ApoE(-/-)Fbn1(C1039G+/-) mice died suddenly, whereas all ApoE(-/-) mice survived. ApoE(-/-)Fbn1(C1039G+/-) mice showed coronary plaques and myocardial infarction (75% of mice). Furthermore, they displayed head tilt, disorientation, and motor disturbances (66% of cases), disturbed cerebral blood flow (73% of cases; MR angiograms) and brain hypoxia (64% of cases), indicative of stroke.. Elastin fragmentation plays a key role in plaque destabilization and rupture. ApoE(-/-)Fbn1(C1039G+/-) mice represent a unique model of acute plaque rupture with human-like complications.

Topics: Animals; Aorta; Apolipoproteins E; Biomarkers; Brachiocephalic Trunk; Cardiomegaly; Carotid Artery, Common; Cerebrovascular Circulation; Death, Sudden; Diet, Western; Disease Models, Animal; Elastin; Female; Fibrillin-1; Fibrillins; Hemorrhage; Hypoxia, Brain; Mice; Microfilament Proteins; Microvessels; Myocardial Infarction; Neovascularization, Pathologic; Nervous System Diseases; Plaque, Atherosclerotic; Rupture, Spontaneous; Stroke; Ventricular Dysfunction, Left

Thoracic aortic rupture and aortopulmonary fistulation are rare conditions in horses. It mainly affects Friesian horses. Intrinsic differences in biomechanical properties of the aortic wall might predispose this breed. The biomechanical and biochemical properties of the thoracic aorta were characterized in warmblood horses, unaffected Friesian horses and Friesians with aortic rupture in an attempt to unravel the underlying pathogenesis of aortic rupture in Friesian horses. Samples of the thoracic aorta at the ligamentum arteriosum (LA), mid thoracic aorta (T1) and distal thoracic aorta (T2) were obtained from Friesian horses with aortic rupture (A), nonaffected Friesian (NA) and warmblood horses (WB). The biomechanical properties of these samples were determined using uniaxial tensile and rupture assays. The percentages of collagen and elastin (mg/mg dry weight) were quantified.. Data revealed no significant biomechanical nor biochemical differences among the different groups of horses. The distal thoracic aorta displayed an increased stiffness associated with a higher collagen percentage in this area and a higher load-bearing capacity compared to the more proximal segments.. Our findings match reported findings in other animal species. Study results did not provide evidence that the predisposition of the Friesian horse breed for aortic rupture can be attributed to altered biomechanical properties of the aortic wall.

Topics: Animals; Aorta, Thoracic; Aortic Rupture; Collagen; Elastin; Female; Horse Diseases; Horses; Male; Rupture, Spontaneous; Tensile Strength

We present a 3-year-old boy with an elastin gene mutation and multiple peripheral pulmonary stenoses, who developed aneurysms of the pulmonary arteries spontaneously. We performed transcatheter occlusion of the aneurysms with detachable coils. While pulmonary arterial aneurysms may develop following pulmonary balloon angioplasty, spontaneous development is exceedingly rare. To the best of our knowledge, this is the first report describing spontaneous development of pulmonary artery aneurysms in a patient with peripheral pulmonary artery stenoses due to mutation of the elastin gene or Williams-Beuren syndrome.

Topics: Aneurysm, Ruptured; Angiography; Arterial Occlusive Diseases; Cardiac Catheterization; Child, Preschool; DNA; Elastin; Embolization, Therapeutic; Follow-Up Studies; Humans; Male; Mutation; Pulmonary Artery; Rupture, Spontaneous; Tomography, X-Ray Computed; Williams Syndrome

The occurrence of intracranial aneurysms and of aneurysmal subarachnoid hemorrhage are influenced by genetic factors. Recent genomic studies in Japan have defined 3 chromosomal loci and 1 haplotype of elastin polymorphisms as important risk factors, both for affected sib pairs and sporadic patients.. We have genotyped 2 single nucleotide polymorphisms in the elastin gene and evaluated their allelic association with intracranial aneurysm in a Central European sample of 30 familial and 175 sporadic patients and 235 population controls.. We found no allelic association between this elastin polymorphism haplotype and intracranial aneurysm.. Our data probably reflect increased genetic heterogeneity of intracranial aneurysm in Europe compared with Japan.

Topics: Adult; Age of Onset; Alleles; Aneurysm, Ruptured; Austria; Chromatography, High Pressure Liquid; DNA Mutational Analysis; Elastin; Female; Genetic Heterogeneity; Genetic Predisposition to Disease; Germany; Haplotypes; Humans; Intracranial Aneurysm; Japan; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Rupture, Spontaneous; Subarachnoid Hemorrhage

Because spontaneous rupture of hepatocellular carcinoma (HCC) is one kind of bleeding complication related to the blood vessels, the possible mechanism of this rupture should occur on the blood vessel itself. Our hypothesis, which has not yet been investigated, is that the vascular integrity of HCC might be damaged during vascular injury.. We examined semiquantitatively the expression of von Willebrand factor, elastin, neutrophil elastase, type IV collagen, and collagenase in 23 specimens of HCC with spontaneous rupture by immunohistochemistry, and compared them with 30 specimens of HCC without rupture.. There was a significant decrease of von Willebrand factor, proliferation of degenerated elastin, abnormal distribution of neutrophil elastase, degradation of type IV collagen, and increase in collagenase production around the blood vessels in ruptured HCC. Since the decreased expression of von Willebrand factor is an indicator of vascular injury and elastase and collagenase are present in inflammatory processes, we postulate that the vascular injury probably exists before spontaneous rupture of HCC occurs. The blood vessel dysfunction resulting from the degeneration of elastin and the degradation of type IV collagen can render the blood vessels stiff and weak, causing them to split easily when the vascular load increases from hypertension or minor mechanical trauma.. Spontaneous rupture of HCC may be related to the vascular dysfunction.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Case-Control Studies; Collagen; Collagenases; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Hepatectomy; Humans; Immunohistochemistry; Leukocyte Elastase; Liver; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Partial Thromboplastin Time; Prothrombin Time; Risk Factors; Rupture, Spontaneous; Vascular Diseases; von Willebrand Factor

Aneurysms are morphologically classified as true or false based on the nature of their walls. True aneurysms are composed of all or parts of layers of the vessel. False aneurysms are the result of rupture and their walls have only fibrous tissues. The orifice of false aneurysms is narrow relative to the aneurysmal diameter and thus they are grossly or angiographically referred to as punched-out lesions. Hence false aneurysms present with punched-out lesions, but in reverse, are all of punched-out lesions false aneurysms? We experienced some cases of punched-out lesions which histologically contained traces of elastin, and the purpose of this report was to histologically investigate grossly punched-out lesions. We examined 671 elderly autopsy cases, and a total of 21 grossly punched-out lesions in the aorto-iliac region were selected. They were histologically classified as false, "pseudo-false", or "disguised" aneurysm. False aneurysms were found in 3 patients (0.45%), and were histologically mycotic. A total of 5 "pseudo-false" aneurysms were found in 3 patients (0.45%). They histologically contained traces of elastin, and thus they were categorised in true aneurysms. A total of 13 "disguised" aneurysms were found in 6 patients (0.89%). They were true fusiform aneurysms with an eccentric thrombus, on which a fibrin-cap formed a narrow orifice. Partial sections are insufficient for diagnosis; cross-sections are necessary. To the best of our knowledge, there have been no reports of "pseudo-false" or "disguised" aneurysms in the aorto-iliac region.

Topics: Aged; Aged, 80 and over; Aneurysm, False; Aneurysm, Infected; Aneurysm, Ruptured; Aortic Aneurysm, Abdominal; Elastin; Female; Humans; Iliac Aneurysm; Immunohistochemistry; Male; Retrospective Studies; Rupture, Spontaneous

The spontaneous rupture of the internal elastic lamina (IEL) in various arteries occurs to different extents in different rat strains. We have quantified this phenomenon in the caudal and renal arteries and abdominal aorta in two normotensive inbred strains: the Brown Norway (BN) and Long Evans (LE) strains. At 5 weeks of age, BN rats of both sexes exhibited small numbers of interruptions in the IEL of the caudal artery, whereas LE rats did not. Postpubertal male and female BN rats presented large numbers of IEL interruptions in the caudal artery and significant numbers in the renal artery and abdominal aorta, whereas LE rats showed few in the caudal artery and none in the other arteries. Treatment with beta-aminopropionitrile (BAPN, an inhibitor of lysyl oxidase, the enzyme involved in the formation of cross-links in elastin and collagen) increased the formation of IEL ruptures in both strains in the caudal and renal artery and in the abdominal aorta in BN rats, but not in the abdominal aorta of LE rats. Apart from IEL ruptures, which were more prevalent in BN rats, no differences were observed in the ultrastructure of the aortic elastic fibers between the two strains, either in controls or in BAPN-treated rats. When male rats of both strains were made hypertensive by unilateral nephrectomy and administration of deoxycorticosterone and salt, mortality was more precocious in the BN strain although blood pressure was significantly higher in the BN strain at only one time point. The incidence of cerebrovascular hemorrhage was 48% in BN rats and 0% in LE rats. Hypertension increased the formation of ruptures in the IEL in some arteries - to a greater extent in the BN than in the LE rats. These results raise the possibility that the propensity to spontaneous rupture of the IEL, which is in part genetically determined, may reflect a latent form of vascular fragility which becomes significant in hypertension, resulting in poor survival and susceptibility to cerebrovascular accidents.

Topics: Aminopropionitrile; Aneurysm; Animals; Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Hypertension; Longevity; Male; Protein-Lysine 6-Oxidase; Rats; Rats, Inbred BN; Rupture, Spontaneous; Species Specificity; Vascular Diseases

Topics: Animals; Aortic Valve; Aortic Valve Insufficiency; Cartilage; Cattle; Collagen; Connective Tissue; Elastin; Formaldehyde; Humans; Lymphocytes; Necrosis; Rupture, Spontaneous; Swine; Transplantation, Heterologous

Topics: Adult; Collagen; Connective Tissue; Ehlers-Danlos Syndrome; Elastic Tissue; Elastin; Histocytochemistry; Humans; Lysine; Male; Microscopy, Electron; Renal Artery; Rupture, Spontaneous; Skin; Vascular Diseases