Accelerated intimal hyperplasia and increased endogenous inhibitors for NO synthesis in rabbits with alloxan-induced hyperglycaemia. (1/1322)
1. We examined whether endogenous inhibitors of NO synthesis are involved in the augmentation of intimal hyperplasia in rabbits with hyperglycaemia induced by alloxan. 2. Four weeks after the endothelial denudation of carotid artery which had been performed 12 weeks after alloxan, the intimal hyperplasia was greatly augmented with hyperglycaemia. The degree of hyperplasia was assessed using three different parameters of histopathological findings as well as changes in luminal area and intima: media ratio. 3. There were positive and significant correlations between intima:media ratio, plasma glucose, and concentrations of N(G)-monomethyl-L-arginine (L-NMMA) and N(G), N(G)-dimethyl-L-arginine (ADMA) in endothelial cells, that is, the intima:media ratio became greater as plasma glucose and endothelial L-NMMA and ADMA were increased. Furthermore, endothelial L-NMMA and ADMA were increased in proportion to the increase in plasma glucose. 4. In contrast, there were inverse and significant correlations between cyclic GMP production by carotid artery strips with endothelium and plasma glucose, between cyclic GMP production and endothelial L-NMMA and ADMA, and between the intima:media ratio and cyclic GMP production. 5. Exogenously applied L-NMMA and ADMA inhibited cyclic GMP production in a concentration-dependent manner. IC50 values were determined to be 12.1 microM for the former and 26.2 microM for the latter. The cyclic GMP production was abolished after the deliberate removal of endothelium from the artery strips. 6. These results suggest that the augmentation of intimal hyperplasia with hyperglycaemia is closely related to increased accumulation of L-NMMA and ADMA with hyperglycaemia, which would result in an accelerated reduction in NO production/release by endothelial cells. (+info)Blood-borne tissue factor: another view of thrombosis. (2/1322)
Arterial thrombosis is considered to arise from the interaction of tissue factor (TF) in the vascular wall with platelets and coagulation factors in circulating blood. According to this paradigm, coagulation is initiated after a vessel is damaged and blood is exposed to vessel-wall TF. We have examined thrombus formation on pig arterial media (which contains no stainable TF) and on collagen-coated glass slides (which are devoid of TF) exposed to flowing native human blood. In both systems the thrombi that formed during a 5-min perfusion stained intensely for TF, much of which was not associated with cells. Antibodies against TF caused approximately 70% reduction in the amount of thrombus formed on the pig arterial media and also reduced thrombi on the collagen-coated glass slides. TF deposited on the slides was active, as there was abundant fibrin in the thrombi. Factor VIIai, a potent inhibitor of TF, essentially abolished fibrin production and markedly reduced the mass of the thrombi. Immunoelectron microscopy revealed TF-positive membrane vesicles that we frequently observed in large clusters near the surface of platelets. TF, measured by factor Xa formation, was extracted from whole blood and plasma of healthy subjects. By using immunostaining, TF-containing neutrophils and monocytes were identified in peripheral blood; our data raise the possibility that leukocytes are the main source of blood TF. We suggest that blood-borne TF is inherently thrombogenic and may be involved in thrombus propagation at the site of vascular injury. (+info)Studies on structural changes of the carotid arteries and the heart in asymptomatic renal transplant recipients. (3/1322)
BACKGROUND: The present study was designed to characterize early structural changes of large arteries in renal transplant recipients with no clinical evidence of cardiovascular disease and normal blood pressure values, and to analyse the relationship between arterial alterations and those of the heart. METHODS: Intima media thickness and atherosclerotic plaques of the carotid arteries as well as left ventricular geometry and function were examined in 35 asymtomatic renal transplant recipients and 29 age- and sex-matched healthy controls by high resolution B-mode ultrasound and by echocardiography. RESULTS: Intima-media thickness of the carotid arteries was significantly higher in renal transplant recipients (1.21+/-0.08 mm) than in healthy controls (0.74+/-0.04 mm) (P<0.001). Atherosclerotic plaques were found in the majority of renal transplant recipients (71% vs 14% in healthy controls, P<0.001). Left ventricular mass index was significantly increased in the group of renal transplant recipients (264+/-13 g, 146+/-7 g/m2) when compared with healthy controls (155+/-8 g, 83+/-4 g/m2) (P<0.001). Multiple regression analysis in renal transplant recipients showed that intima media thickness of the carotid arteries was significantly related to left ventricular mass index (P<0.02), but not to age, blood pressure, body mass index, serum creatinine, cholesterol and lipoprotein (a) levels. In the group of healthy controls, intima-media thickness of the carotid artery was related to age (P<0.002), but not to left ventricular mass index or the other independent variables. CONCLUSIONS: The present study documents pronounced intima-media thickening in asymptomatic renal transplant recipients. Atherosclerotic lesions are present in most renal transplant recipients with no clinical evidence of cardiovascular disease. We observed a parallelism between arterial wall thickening and left ventricular hypertrophy, although blood pressure levels were normal during haemodialysis therapy and after renal transplantation. (+info)Arterial damage induced by cryopreservation is irreversible following organ culture. (4/1322)
OBJECTIVES: The aim of the present study was to investigate the changes which occur to the arterial wall following cryopreservation and thawing and to determine whether these changes are reversible after a week of culture in an organ bath. MATERIALS AND METHODS: Rat iliac arterial segments were cryopreserved. Once thawed, the arterial segments were cultured for a period of 0, 1, 2, 4 or 7 days. Freshly isolated rat iliac vessels cultured for 7 days served as the control group. Evaluation was made of ultrastructural changes, the expression of metalloproteinase activity (MMP-1, MMP-3 and MMP-9) and the apoptotic state of cells. RESULTS: The freezing-thawing process induced damage to the arterial segments compared to fresh control vessels. After 1 week of culture, arteries showed a high degree of tissue degeneration. Only a few individual endothelial cells remained on the luminal surface. There was a gradual increase in the proportion of apoptotic cells. The sequential expression of MMP-1 during the first 2 days and subsequent expression of MMP-3 and MMP-9 were of most significance. CONCLUSIONS: Cryopreservation induced damage to the vessels which could not be reversed by organ culture. The changes observed in the expression of metalloproteinases may be indicative of the degenerative process which occurs in the extracellular matrix. (+info)Cross-sectional and 4-year longitudinal associations between brachial pulse pressure and common carotid intima-media thickness in a general population. The EVA study. (5/1322)
BACKGROUND AND PURPOSE: The cross-sectional and 4-year longitudinal associations between brachial pulse pressure (PP) and ultrasound measurements of common carotid intima-media thickness (CCA-IMT) were assessed. METHODS: A population of 957 volunteers aged 59 to 71 years was recruited from the electoral rolls of the city of Nantes (western France) and reexamined 4 years later. Longitudinal changes in PP and CCA-IMT were computed as the difference between 4-year follow-up and baseline values. RESULTS: Baseline CCA-IMT and PP were positively associated in both age- and sex-adjusted analysis (partial correlation coefficient=0.20, P<0.001) and in multivariate analysis adjusted for traditional cardiovascular risk factors and mean blood pressure (partial correlation coefficient=0.18, P<0.001). In longitudinal analysis, baseline PP was associated with the change in 4-year CCA-IMT (partial correlation coefficient=0.11, P<0.001), and baseline CCA-IMT was a predictor of the 4-year change in PP (partial correlation coefficient=0.10, 0.001+info)