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PubMed2005

Pleiotropic effects of statins in atherosclerosis: role on endothelial function, inflammation and immunomodulation.

Atherosclerosis and its complications still represent the major cause of death in developed countries. Statins have been described as the most potent class of drugs to reduce serum cholesterol levels. The effectiveness and rapidity of statin-induced decreases in coronary events led to the speculation that statins possess also cholesterol-independent effects. By the inhibition of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol synthesis, statins reduce not only cholesterol but also non steroidal isoprenoid intermediates production. Since these isoprenoids, such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate, regulate the small signaling proteins, Ras and Rho, inhibition of these prenylated proteins by statins might account for their non-lipid-related effects. In this review, we describe the numerous beneficial pleiotropic effects of statins that could modulate atherogenesis.

Arteriosclerosis↗
PubMed2005

[Effect of fosinopril on some parameters of endothelial function in patients with metabolic syndrome].

Angiotensin converting enzyme inhibitor fosinopril was given for 12 weeks to 92 patients with hypertension and metabolic syndrome. Spectra of carbohydrates and lipids, blood plasma kallikrein-kinin and prostacyclin-thromboxane systems, vascular endothelium dependent vasodilating function were studied in all patients. Hypertension was accompanied with lowering of endothelium dependent vasodilation which degree correlated with lowering of prostacyclin and elevation of thromboxane levels, dys-balance of kallikrein-kinin system as well as with severity of hypertension and metabolic syndrome. Effective blood pressure lowering caused by therapy with fosinopril was associated with stabilization of parameters of kallikrein-kinin and prostacyclin-thromboxane systems, improvement of endothelium dependent vasodilation.

Adult↗
PubMed2006

Elevated levels of brain natriuretic peptide as a predictor of impaired coronary endothelial function in patients with left ventricular remodeling.

BACKGROUND: Plasma levels of brain natriuretic peptide (BNP) correlate with left ventricular remodeling, but the relationship between BNP induction and coronary function remains unclear. OBJECTIVES: The present study assessed BNP production in response to left ventricular enlargement and investigated the relationship between BNP production and coronary vasodilating function in patients with left ventricular remodeling. METHODS: Patients (n = 63) with normal or mildly diseased coronary arteries underwent Doppler flow study of the left anterior descending coronary artery. Vascular reactivity was examined using intracoronary acetylcholine, papaverine and nitroglycerin using a Doppler guidewire. RESULTS: Left ventricular end-diastolic dimension was positively correlated with BNP (r = 0.45, p < 0.001) in all patients. BNP was significantly and inversely correlated with percentage change in coronary artery diameter induced by acetylcholine (r = -0.56, p < 0.001) but not by nitroglycerin (r = -0.20, p = 0.28) in patients with left ventricular end-diastolic dimension > or = 55 mm (n = 32). By contrast, BNP was not significantly correlated with percentage change in coronary artery diameter induced by either acetylcholine or nitroglycerin in patients with left ventricular end-diastolic dimension < 55 mm (n = 31). Further, BNP was not correlated with the percentage change in coronary blood flow induced by acetylcholine or by papaverine in patients with or without left ventricular remodeling. CONCLUSIONS: The elevation in plasma BNP levels that occurs in association with left ventricular enlargement is a predictor of impaired endothelium-dependent vasodilation in conductance coronary arteries.

Adult↗
PubMed2006

[Effect of nebivolol on endothelial function in obese patients with hypertension].

The study aimed at assessing functional state of vessel endothelium using Doppler cardiography in patients with arterial hypertension and excessive weight under Nebivolol treatment. 15 overweight patients with hypertension disease who underwent Tselemayer-Sorensena test have been observed to assess endothelium-dependent and endothelium-independent vasodilatation. Positive influence of nebivolol on vessel endothelium was noted in the study.

Aged↗
PubMed2006

Brachial endothelial function in subjects with familial combined hyperlipidemia and its relationships to carotid artery intima-media thickness.

AIM: The aim of this study was to quantify the flow-mediated dilatation (FMD) of brachial artery in asymptomatic members of families with familial combined hyperlipidemia (FCH) and to determine the relation between FMD and risk factors accompanying FCH. We also investigated the association between FMD and the intima-media thickness (IMT) of the common carotid artery. METHODS: Eighty-two members of 29 FCH families were divided into two groups: probands and hyperlipidemic first-degree relatives (HL) (n=47) and normolipidemic first-degree relatives (NL) (n=35). The control (C) groups, C-HL (n=20) and C-NL (n=20), consisted of sex- and age-matched healthy individuals. FMD was assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia. RESULTS: Both hyperlipidemic subjects and their NL had significantly lower FMD (3.4+/-3% vs 6.3+/-2.8%, P<0.001, 5.2+/-2.3% vs 7.8+/-2.8%, P<0.01, respectively) compared to controls. In multivariate backward stepwise regression analysis, FMD in members of FCH families was independently associated with sex (P<0.001), age (P<0.01), C-peptide (P<0.05) and borderline with glycemia (P=0.052). FMD correlated inversely with IMT in all subjects of FCH families and in hyperlipidemic members. In multivariate backward stepwise regression analysis this relation remained independent (P<0.001, P<0.01, respectively). CONCLUSIONS: Members of FCH families showed impaired FMD, which was independently associated with markers of insulin resistance. FMD and IMT were independently associated in hyperlipidemic, but not in normolipidemic members of FCH families.

Adult↗
PubMedDate not supplied

Alterations of the endothelial function of isolated aortae in rats with adjuvant arthritis.

Adjuvant arthritis was induced in 30 male Wistar rats by injection into the tail of heat-killed Mycobacterium butyricum. Three weeks later, 14 of these rats exhibited severe arthritic lesions. Their thoracic aortae were studied in parallel with those isolated from a control group. On rings precontracted with phenylephrine (0.1 microM), the endothelium-dependent relaxations produced by acetylcholine and histamine were significantly diminished in the arthritic group as compared to the control group. Moreover, the increase in tone induced by incubation with methylene blue (10 microM) (a nonspecific inhibitor of endothelium-derived relaxing factor) was significantly less pronounced in preparations isolated from the arthritic group. On the other hand, relaxations produced by the endothelium-independent vasodilators verapamil and nitroprusside were similar in both groups. It is concluded that adjuvant arthritis modifies the endothelium-derived relaxing factor-mediated responses of rat aorta.

Acetylcholine↗