Vascular wall remodeling in patients with supravalvular aortic stenosis and Williams Beuren syndrome.
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Supravalvular aortic stenosis (SVAS) and Williams Beuren syndrome (WBS) can be considered as inherited diseases affecting the whole arterial tree and causing narrowing of the vessels. It has been reported that abnormal deposition of elastin in arterial walls of patients with SVAS and WBS leads to increased proliferation of arterial smooth muscle cells (SMC), which result in the formation of hyperplastic intimal lesions. In this work, we conducted morphological and morphometrical analysis with stenotic aortas from patients suffering from SVAS and WBS and from healthy control subjects and demonstrated that the amount of elastic fibers and the loss of integrity of vascular elastic fibers in the aortas reflect similar changes in the skin of patients with SVAS or WBS, as reported in our previous work conducted on skin in these pathological states. On the other hand, we conducted investigations on metalloproteinases (MMP2, MMP9, MMP7) and their specific tissue inhibitors TIMP1 and TIMP2 to verify their possible involvement in the etiopathogeny of SVAS and WBS. We particularly evidenced an altered MMP9/TIMP1 balance in favor of matrix degradation which could facilitate SMC migration and neointimal hyperplasia. Our findings suggest that elastinolytic enzymes secreted by arterial SMC, possibly including matrilysin 1, are critical for the development of arterial lesions in SVAS and WBS and contribute to perpetuate arterial stenosis in either SVAS or WBS. (+info)
Left ventricular apical aneurysm as a consequence of diffuse type congenital nonfamilial supravalvular aortic stenosis in a 30-year-old female.
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Congenital nonfamilial supravalvular aortic stenosis (SVAS) is relatively rare, its diffuse type being the least common. We present a 30-year-old woman with diffuse SVAS complicated with left ventricular apical aneurysm. We believe that subtle left ventricular myocardial ischemia or infarction and long-lasting severe pressure overload to the apical chamber caused LV apical aneurysm in our case. Acquired LV apical aneurysm secondary to supravalvular aortic stenosis, in the absence of atherosclerotic coronary artery disease and hypertrophic obstructive cardiomyopathy, has not been described before. (+info)
Valvular and supravalvular aortic stenosis in heterozygous familial hypercholesterolemia, a case report.
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Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by a high level of LDL-cholesterol and frequent coronary atherosclerosis. We studied a 64 year old woman with heterozygous (hetero) FH, who showed symptoms of chest pain and dyspnea with no other coronary risk factors than post-menopause and hypercholesterolemia. Although her coronary symptoms didn't reveal significant stenosis on coronary angiography, she had severe aortic valvular and supravalvular stenosis at the ascending aorta, which qualified her for aortic valve replacement. Moreover, a coronary flow study revealed functional ischemia with a reduction of the coronary flow reserve. We report a case of valvular and supravalvular aortic stenosis corrected by aortic valve replacement, a rare complication of hetero FH. (+info)
Domains 16 and 17 of tropoelastin in elastic fibre formation.
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Naturally occurring mutations are useful in identifying domains that are important for protein function. We studied a mutation in the elastin gene, 800-3G>C, a common disease allele for SVAS (supravalvular aortic stenosis). We showed in primary skin fibroblasts from two different SVAS families that this mutation causes skipping of exons 16-17 and results in a stable mRNA. Tropoelastin lacking domains 16-17 (Delta16-17) was synthesized efficiently and secreted by transfected retinal pigment epithelium cells, but showed the deficient deposition into the extracellular matrix compared with normal as demonstrated by immunofluorescent staining and desmosine assays. Solid-phase binding assays indicated normal molecular interaction of Delta16-17 with fibrillin-1 and fibulin-5. However, self-association of Delta16-17 was diminished as shown by an elevated coacervation temperature. Moreover, negative staining electron microscopy confirmed that Delta16-17 was deficient in forming fibrillar polymers. Domain 16 has high homology with domain 30, which can form a beta-sheet structure facilitating fibre formation. Taken together, we conclude that domains 16-17 are important for self-association of tropoelastin and elastic fibre formation. This study is the first to discover that domains of elastin play an essential role in elastic fibre formation by facilitating homotypic interactions. (+info)
Relative role of left ventricular geometric remodeling and of morphological and functional myocardial remodeling in the transition from compensated hypertrophy to heart failure in rats with supravalvar aortic stenosis.
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OBJECTIVE: To evaluate the relative contribution of left ventricular (LV) geometric remodeling and of morphological and functional myocardial changes in rats with induced supravalvar aortic stenosis (SAS), in the transition from compensated hypertrophy to congestive heart failure (CHF). METHODS: Twenty one weeks after induction of SAS, the rats were classified as controls (CG, n=13), without congestive heart failure (SG, n=11), or with congestive heart failure (SG-HF, n=12). All groups were evaluated with echocardiographic, hemodynamic and morphological study of the myocardium. RESULTS: Twenty one weeks after SAS: mass index (SG-HF>SG>CG, p<0.05); systolic pressure (SG-HF= SG>CG, p<0.05); diastolic pressure (SG-HF>SG>CG, p<0.05); systolic and diastolic meridional stress (SG-HF>SG>CG, p<0.05); LV myocyte cross-sectional area (SG-HF>SG>CG, p<0.05) and hydroxyproline content (SG-HF>SG>CG, p<0.05). In the SG-HF group, LV geometric remodeling was characterized by a significant increase in dimensions and relative thickness of the normal wall (excentric remodeling), whereas the SG group presented a concentric remodeling. Indexes of LV performance in the SG-HF group were significantly lower than those of the SG group. CONCLUSION: The SG-HF and SG groups differed primarily in the LV geometric remodeling and structural myocardial remodeling process, which established a chronically compensated state in the SG group and triggered CHF in the SG-HF group in the presence of equivalent degrees of impaired contractility. (+info)
Prevalence and prediction of renal artery stenosis in patients with coronary and supraaortic artery atherosclerotic disease.
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BACKGROUND: Renal atherosclerosis is associated with increased cardiovascular mortality. This study aimed to determine the prevalence and predictors of renal artery stenosis (RAS) in patients with coronary artery disease (CAD) and supraaortic arteries (SA) stenosis. METHODS: Renal angiography was performed in 1193 (807 men) consecutive patients referred for coronary or SA angiography. Group I included 296 (136 men, 60.1 +/- 9.5 years) patients with no significant (< 50%) lesion in coronary arteries or SA; group II included 706 (526 men, 62.2 +/- 9.7 years) patients with stenosis > or = 50% within single arterial territory (coronary arteries or SA) and group III included 191 (145 men, 64.9 +/- 8.5 years) patients with stenosis > or = 50% in both territories. RESULTS: Some RAS was found in 55 (18.6%) patients in group I, 250 (35.4%) patients in group II and 115 (60.2%) patients in group III (P < 0.001). The proportion of patients with RAS > or = 50% in groups I, II and III was 3.3, 6.2 and 18.3%, respectively (P < 0.001). RAS prevalence increased with the number of stenosed coronary arteries (38.4% in 1-vessel, 42.1% in 2-vessel, 48.5% in 3-vessel CAD, P < 0.001). Independent predictors of RAS > or = 50% identified by logistic regression analysis were SA stenosis [relative risk (RR) = 3.28, P < 0.001], 2-3-vessel-CAD (RR = 2.04, P = 0.002), creatinine level > or = 1.07 mg/dl (RR = 2.95, P < 0.001), hypertension (RR = 2.97, P = 0.012) and body mass index < 25 kg/m(2) (RR = 1.42, P = 0.169). A calculated score for RAS > or = 50% prediction (based on the regression model) was reliable (coefficient of determination, R = 0.978) and showed a sensitivity of 77.5% and a specificity of 63.9%. CONCLUSIONS: RAS prevalence and severity increases with the number of arterial territories involved and CAD severity. The following independent predictors of RAS > or = 50% were identified: SA involvement, 2-3-vessel-CAD, serum creatinine level and hypertension. (+info)
Cardiovascular spectrum in Williams-Beuren syndrome: the Mexican experience in 40 patients.
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In this study, we have identified and evaluated the cardiovascular anomalies associated with Williams-Beuren syndrome in children.In a retrospective, lineal, and observational study, we reviewed the files of children who were seen from 1980 through 2005 (25 years) after a clinical diagnosis of Williams-Beuren syndrome.Forty children were diagnosed with this syndrome at the National Institute of Pediatrics in Mexico City. Of these, 32 (80%) were found to have congenital heart defects. The male-to-female ratio was 1.3:1 and ages ranged from 6 months to 15 years (mean, 4.4 years) at the time of diagnosis. All of the patients had morphologic and genetic characteristics typical of the syndrome.We emphasize the cardiovascular aspects from a clinical point of view. Supravalvular aortic stenosis was our most frequent finding, in 18 of 32 patients (56%); gradient differences in these patients ranged from 14 to 81 mmHg. Five patients showed combined lesions, the most frequent being supravalvular aortic stenosis in combination with pulmonary artery brachial stenosis, or with atrial and ventricular defects. Patients with incomplete atrioventricular defect and bicuspid aortic valve, as were seen at our hospital, have not to our knowledge been reported in other studies.One of the patients was scheduled for balloon dilation; another was scheduled for surgery; a 3rd patient was operated on twice for the placement of an aorto-aortic bridge; another underwent ventricular septal defect closure; and yet another underwent aortoplasty, this last dying shortly after surgery. (+info)
Surgical repair of supravalvular aortic stenosis with use of Brom's technique: short-term results in 9 children.
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There are few published reports of the results of supravalvular aortic stenosis correction with the use of Brom's 3-patch technique. Herein, we report our use of this procedure and the short-term results therefrom.From 2002 through 2007, 9 children underwent surgical correction of localized supravalvular aortic stenosis at our hospital. The patients ranged in age from 5 to 14 years, and 8 had Williams syndrome. All operations were performed by the same surgical team.No clinically significant associated cardiac anomalies were encountered. Each aortic repair involved the use of pericardium, Dacron, or both. One patient had an uncorrected right coronary artery obstruction and died postoperatively of refractory supraventricular tachycardia. In all 8 patients who survived, postoperative transaortic blood pressure gradients were improved (range, 0-16 mmHg), and no repeat operations were needed after 6 to 55 months' follow-up.We consider Brom's technique to be safe in the repair of supravalvular aortic stenosis. In our limited series, it produced effective anatomic restoration, with good short-term and potentially good long-term results. (+info)