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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors retrospectively analyzed the prevalence of renal artery stenosis in 63 consecutive patients with aortic dissection who underwent thoracic and abdominal aortography. Ten patients (16%) had renal artery stenosis, five with atherosclerosis and five with fibromuscular lesions. Risk factors for aortic dissection were Marfan disease in nine patients, bicuspid aortic valve in one, and hypertension in 54 (including seven patients with Marfan syndrome). If the patients with Marfan syndrome and the patient with the bicuspid aortic valve are excluded, renal artery stenosis was present in 10 of 53 patients (19%) when the cause of dissection was presumably hypertension. This finding suggests that renovascular hypertension is a greater risk factor for aortic dissection than is essential hypertension. The success of angiotensin converting enzyme inhibitors and percutaneous transluminal renal angioplasty (PTRA) in controlling renovascular hypertension has been proved. In this series, emergent PTRA successfully controlled the hypertension in one patient with a type B dissection, resulting in an excellent clinical outcome. Angiography should be routinely performed on patients with aortic dissections to evaluate for renal artery stenosis.
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PMID:Renal artery stenosis in patients with aortic dissection: increased prevalence. 205 16

Clear evidence has not yet come concerning the genetics of abdominal aortic aneurysms (AAA). There are circumstantial proof for a hereditary predisposition. In a retrospective study of sixty patients consecutively underwent a surgical repair for AAA, showed that one third of them knew a first-degree relative with the same disease. Environmental factors, such as smoking, ageing or hypertension, must be taken into account. A multifactorial mode of inheritance is under discussion due to both multiple genes with different expressivity and diverse environmental factors. Linkage-analysis or DNA sequencing of the different gene loci in population studies or sibbling-analysis are the tools in search for candidate genes for inheritance of AAA. Mutations in those genes encoding structural components of the aortic wall, such as collagen-type-III, fibrillin or elastin, are not taken to be the underligned genetic cause. Mutations in genes encoding enzymes for the turnover of the aortic wall components, such as alpha-1-antitrypsin or matrix-metalloproteinase-2, may play an important role.
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PMID:[Mode of genetic inheritance of abdominal aortic aneurysm: still no clear answers]. 758 55

Arterial involvement is an important feature of the diagnosis and, above all, prognosis of heritable disorders of connective tissue. In pseudoxanthoma elasticum, a progressive occlusive syndrome is associated with hemorrhage and especially with gastrointestinal bleeding. Aneurysms are uncommon. Hypertension occurs frequently. Cutaneous signs (yellowish pseudo xanthomatous papules of the large folds) the ocular changes (angioid streaks) and pathology showing numerous, thickened, fragmented, disorganized, calcified elastic fibers in the deep dermis and arterial walls, allow the diagnosis to be made. In the heterogeneous group of Ehlers-Danlos syndromes, type IV is characterized by sudden spontaneous rupture of the large arteries. Aneurysms and carotido-cavernous fistulae are rather frequent. Owing to friability of the arterial walls, arteriograms and other procedure requiring arterial puncture may prove hazardous and surgery difficult. Such patients have an acrogeric morphotype, and thin, fragile skin, but cutaneous hyperelasticity and joint hyperlaxity are usually minimal. Pathology evidences collagen hypoplasia in the skin and arterial walls. The severity of Marfan syndrome is due to aortic involvement. A fusiform aneurysm of the ascending aorta represents a vital risk of rupture. Aortic root dilatation is associated and responsible of severe aortic regurgitation. Aortic dissection is also a serious threat. Improved surgical techniques for repairing a dilated or dissected aortic root with simultaneous replacement of the aortic valve increases the life expectancy of such patients. Dolichomorphism is the characteristic skeletal abnormality, particularly with arachnodactyly and upward ectopia lentis, which is almost bilateral, is a very frequent feature of Marfan syndrome. The most typical histological finding is aortic cystic median necrosis. The basic defect in Marfan syndrome concerns the fibrillin, whose gene is located on chromosome 15. The three diseases detailed in this paper constitute the main areas of this subject, but arterial involvement may occur in other inheritable disorders of connective tissue (osteogenesis imperfecta, cutis laxa, Werner syndrome, Menkes syndrome, etc).
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PMID:[Arterial involvements in hereditary dysplasia of the connective tissue]. 805 35

Aortic dissection is not a popular disease but it should be listed in the disease to be excluded especially in acute emergent cases, because of its serious and protean clinical manifestations. While DeBakey classification was used over 30 years. Stanford classification is now widely accepted for its clinical availabilities. The features of the aortic dissection are 1) presence of the intimal tear at the proximal end in almost all cases, 2) its frequent location in the ascending aorta and aortic segment just distal to the left subclavian artery, and 3) the dissected plane at the outer media or medial-adventitial border. Systemic hypertension is frequently noticed in cases with aortic dissection. These features suggest hemodynamic effect as a pathogenic factor in addition to mural fragility of the aorta. Aortic dissection is frequently encountered in Marfan syndrome and other heritable diseases of connective tissue. Concerning Marfan syndrome, mutation of fibrillin gene was confirmed. Fibrillin is a microfibril consisting of glycoprotein closely bound to elastin. Therefore, traditional "cystic medial necrosis" which was referred as a principal morphological change corresponding to aortic dissection is now thought to be a secondary change to the aortic injuries occurred in the aortic wall.
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PMID:[Pathology of aortic dissection]. 896 88

A defect in fibrillin integrity predisposes patients with Marfan syndrome to vascular wall abnormalities, most notably aortic rupture and dissection. Renal vascular anomalies have not been described previously in children with Marfan syndrome. In this report, we detail data from a hypertensive 14-year-old girl with clinical stigmata of Marfan syndrome and a diagnostic evaluation significant for characteristic aortic root dilatation and aneurysm, as well as a disparity in renal size and function exacerbated by captopril administration. Renal arteriography confirmed a left main renal artery stenosis that was not amendable to balloon angioplasty. Surgical resection resulted in significant improvement in hypertension. Pathological examination of the resected renal artery segment revealed intimal proliferation, fragmentation of the elastic media, and inner medial dissection. This patient demonstrates that, in addition to the aorta, renal arteries can be affected with the characteristic vascular wall pathology of Marfan syndrome, resulting in systemic hypertension. These data suggest that children with Marfan syndrome and hypertension need to be evaluated carefully for the presence of renal anomalies.
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PMID:Renovascular hypertension in Marfan syndrome. 926 Feb 56

Subarachnoid haemorrhage (SAH) results from leakage of blood into the subarachnoid space and carries high morbidity and mortality. However, there is limited understanding to date, of the risk factors, cellular, intermediate biochemical and genetic traits predisposing to SAH. Nevertheless, in conjunction with improved methods of diagnostic imaging and less invasive approaches to preventing aneurysmal rupture, there may be utility in gaining a better understanding of the pathogenesis and in identifying pre-disease markers. Additionally, it is not impossible that drugs of value (e.g. matrix or endothelial modifiers) could become available. Several different clinical subtypes can be recognised, distinguished by arterial or venous involvement, presence of unruptured arterial aneurysms, and apparently "sporadic" and "familial" occurrences. Epidemiological risk factors include alcohol consumption and smoking: hypertension is a risk factor for rupture. About 10% seem to reflect strong family history and this subset may be particularly illuminating with respect to the molecular pathogenesis. Haemodynamic stress and poor vascular structure may be the main mechanisms of pathogenesis. The epidemiological and statistical evidence for familial megaphenic genes and modifier genes is reviewed. This review focuses on the pathogenesis, as opposed to inflammatory response to SAH. It sets in context the roles of specific genes and their protein products, such as polycystin (PKD1), fibrillin (FBN1), collagen III (COL3A1), elastin (ELN), collagen IV, protease inhibitor or alpha1-antitrypsin (PI) and proteases. These considerations illustrate the shortfalls in current knowledge, the needs of future biochemical and cellular research and their potential implications for future prevention of this often fatal condition.
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PMID:Molecular pathogenesis of subarachnoid haemorrhage. 1279 48

There are significant associations between moderate increases in serum homocysteine and three cardiovascular diseases: ischemic heart disease, deep vein thrombosis and pulmonary embolism, and stroke. An association between the presence of abdominal aortic aneurysm and elevated homocysteine plasma levels has been indicated. Although chronic systemic hypertension is the most common factor predisposing the aorta to dissection, homocysteinemia has never been known as the risk for aortic dissection except for that with Marfan syndrome. Homocysteinemia is suggested to be the risk for aortic dissection in Marfan syndrome and spontaneous cervical artery dissection. Reduced fibrillin-1 deposition into the extracellular matrix is found not only in Marfan syndrome but also in isolated ascending aortic aneurysm and dissection. The reduced matrix deposition produces a mild form of weakness of elastic tissue, which predisposes to ascending aortic aneurysm and dissection in patients who do not have the Marfan syndrome. The defect in fibrillin-1 leads to: (1) formation of elastin that is abnormally aggregated and more easily degraded by matrix metalloproteinases than is normal elastin; (2) upregulation of the synthesis of matrix metalloproteinases; (3) progressive destruction of connective tissue by these enzymes; (4) development of thoracic aortic aneurysms. Homocysteine causes premature breakdown in the arterial elastic fibers by activation of the elastolytic activities. Irreversible homocysteinylation of long-lived proteins should lead to cumulative damage and progressive clinical manifestations, and fibrillin-1 is seen as the paradigm of extracellular connective tissue proteins that are specially susceptible to homocysteine (and presumably homocysteine thiolactone) attack. The authors hereupon propose a novel hypothesis that homocysteine plays an important role in development of aortic dissection and that homocysteinemia is one of the risk factors for aortic dissection.
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PMID:Homocysteinemia is a risk factor for aortic dissection. 1578 May 1

Ramipril improves cardiovascular outcome in patients with peripheral arterial disease; however, the precise mechanisms of benefit remain to be elucidated. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined. In addition, we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture. Forty patients with peripheral arterial disease were randomized to receive ramipril, 10 mg once daily or placebo for 24 weeks. Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index (carotid tonometry and Doppler velocimetry), and regionally via carotid-femoral pulse wave velocity. Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10+/-0.02 mL/mm Hg, (P<0.001, all probability values relative to placebo) and reduced pulse wave velocity by 1.7+/-0.2 m/s (P<0.001), augmentation index by 4.1+/-0.3% (P<0.001), and systolic blood pressure by 5+/-1 mm Hg (P<0.001). Ramipril did not reduce mean arterial pressure significantly compared with placebo (P=0.59). In cell culture, ramiprilat decreased collagen deposition by >50% and increased elastin and fibrillin-1 deposition by >3- and 4-fold respectively (histochemistry and immunohistochemistry). Fibrillin-1 gene expression was increased 5-fold (real-time reverse-transcriptase polymerase chain reaction). Ramiprilat also reduced gene and protein (Western) expression of both matrix metalloproteinase (MMP)-2 and MMP-3. In conclusion, ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation, which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease.
Hypertension 2005 Jun
PMID:Ramipril reduces large-artery stiffness in peripheral arterial disease and promotes elastogenic remodeling in cell culture. 2665 6

Large artery stiffening increases cardiovascular risk and promotes isolated systolic hypertension which is more prevalent in elderly women than men. Variation in sex steroid levels between males and females and throughout life may modulate arterial stiffness. We hypothesized that sex steroids directly influence expression of important structural proteins which determine arterial biomechanical properties. Human aortic smooth muscle cells were incubated with physiological concentrations of 17beta-estradiol, progesterone, 17beta-estradiol and progesterone, or testosterone for 4 weeks. Collagen, elastin, and fibrillin-1 deposition was examined (histochemistry/immunohistochemistry). Gene and protein expression of 2 important matrix metalloproteinases (MMPs), MMPs 2 and 3, regulating matrix turnover was assessed. All sex steroids reduced collagen deposition relative to control (100%). However, the reduction was greater with female sex steroids than testosterone (control, 100%; 17beta-estradiol plus progesterone, 20+/-2%; testosterone 74+/-12%, P<0.001). Female sex steroids increased elastin deposition compared with control (control, 100%; 17beta-estradiol, 540+/-60%; progesterone, 290+/-40%; 17beta-estradiol plus progesterone, 400+/-80%, all P<0.01). The elastin/collagen ratio was >11-fold higher in the presence of 17beta-estradiol and progesterone compared with testosterone. Fibrillin-1 deposition was doubled in the presence of female sex steroids (17beta-estradiol plus progesterone) compared with testosterone (P<0.01). MMP-2 gene and protein expression was unaffected by any sex steroid. Testosterone increased both gene and protein expression of MMP-3 relative to both control and female sex steroids (P<0.01). This may contribute to degradation of elastic matrix proteins. In conclusion, female sex steroids promote an elastic matrix profile, which likely contributes to variation in large artery stiffness observed between sexes and with changes in hormonal status across the lifespan.
Hypertension 2005 Nov
PMID:Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression. 1623 May 20

The microfibrillar protein fibrillin-1 is a component of the mesangial matrix. Defects in fibrillin-1 predisposes individuals to vascular damage in Marfan syndrome, but the role of fibrillin-1 in kidney disease is unknown. We hypothesized that fibrillin-1 is involved in hypertensive or diabetic glomerular disease. DOCA-salt hypertension or streptozotocin (STZ) diabetes led to a significant increase in glomerular fibrillin-1 deposition. To test the functional role of fibrillin-1, DOCA hypertension and STZ diabetes were induced in mice homozygous for a mutation leading to a fivefold lower expression of fibrillin-1 (mgR/mgR). Untreated male mgR/mgR mice usually die from aortic dissection during the first 4 mo of life. All DOCA-treated mgR/mgR mice died within 2 wk after onset of DOCA treatment. DOCA-treated heterozygous (mgR/+) and their wild-type littermates displayed similar blood pressure levels, but albuminuria was significantly lower in mgR/+ than in wild-type mice after DOCA treatment. Similarly, STZ diabetic mgR/mgR and mgR/+ developed lower albuminuria than wild-type mice despite higher blood glucose levels in mgR/mgR and mgR/+ compared with wild-type mice. Blood pressure, blood glucose, and albuminuria did not differ among untreated mgR/mgR, mgR/+, and wild-type mice, respectively. In diabetic mgR/+ and mgR/mgR, but not in wild-type mice, an induction of glomerular decorin expression was observed. Thus underexpression of fibrillin-1 predisposes individuals to lethal aortic dissection in the presence of hypertension. On the other hand, albuminuria as a parameter of microvascular damage in hypertension and diabetes was ameliorated in fibrillin-1-underexpressing mice, possibly due to a compensatory upregulation of decorin. We conclude that fibrillin-1 may contribute to glomerular damage in hypertensive and diabetic kidney disease.
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PMID:Role of fibrillin-1 in hypertensive and diabetic glomerular disease. 1638 Apr 60


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