Interactions between lipoproteins and platelet membranes in obesity.
ABSTRACT The aim was to investigate low-density lipoprotein (LDL) composition and Na(+)/K(+) adenosine triphosphatase (ATPase) and Ca(2+) ATPase activities and membrane fluidity measured by 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in platelets from obese patients and controls in order to identify, if any, platelet membrane's chemical-physical and/or functional modifications associated with compositional modification of circulating lipoproteins. Moreover, we studied the in vitro effect on both platelet transmembrane cationic transport and fluidity, by incubating LDL from 30 obese subjects with platelets from 30 control subjects. The analysis of the chemical composition of LDL from obese patients showed a significant increase in the percent content of total cholesterol (TC) and triglycerides (TGs) and in the mean levels of lipid hydroperoxides compared to controls' LDL. Platelet Na(+)/K(+) ATPase and Ca(2+) ATPase activities showed, respectively, a significant decrease and increase in patients compared to controls; minor significant, respectively, decreases and increases are shown also in control platelets incubated with LDL from obese patients. Anisotropy tested with TMA-DPH probe was significantly increased both in platelets from obese patients and in control platelets incubated with LDL from obese patients compared to control platelets. This study highlights that obesity induces remarkable modifications both in lipoproteins and platelets. Both platelet hyperfunction and quantitative/qualitative alterations in plasma lipoproteins, as well as an altered interaction between circulating lipoproteins and platelets, might play a relevant role in the increased prevalence of the early atherosclerotic lesions development in obese subjects. The present data point out that obesity might represent a major potentially modifiable risk factor for the onset of numerous complications, in particular cardiovascular ones.
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ABSTRACT: Several epidemiological studies have reported that the regional distribution of body fat is a significant and independent risk factor for cardiovascular disease (CVD) and related mortality. Although these associations are well established, the causal mechanisms are not fully understood. Numerous studies have, however, shown that specific topographic features of adipose tissue are associated with metabolic complications that are considered as risk factors for CVD such as insulin resistance, hyperinsulinemia, glucose intolerance and type II diabetes mellitus, hypertension, and changes in the concentration of plasma lipids and lipoproteins. The present article summarizes the evidence on the metabolic correlates of body fat distribution. Potential mechanisms for the association between body fat distribution, metabolic complications, and CVD are reviewed, with an emphasis on plasma lipoprotein levels and plasma lipid transport. From the evidence available, it seems likely that subjects with visceral obesity represent the subgroup of obese individuals with the highest risk for CVD. Although body fat distribution is now considered as a more significant risk factor for CVD and related death rate than obesity per se, further research is clearly needed to identify the determinants of body fat distribution and the causal mechanisms involved in the metabolic alterations. It appears certain, however, that an altered plasma lipid transport is a significant component of the relation between body fat distribution and CVD.Arteriosclerosis (Dallas, Tex.) 10(4):497-511.
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ABSTRACT: We tested the hypothesis that an increase in spontaneous aggregability of platelets in vitro predicts mortality and coronary events in patients who have survived a recent myocardial infarction. A cohort of 149 survivors of infarction entered our study three months after the index infarction and was followed for five years. At entry and at intervals of six months, spontaneous platelet aggregation (SPA) was tested and graded as positive (aggregation within 10 minutes), intermediate (aggregation after 10 to 20 minutes), or negative (no aggregation within 20 minutes). During follow-up, 6.4 percent (6 of 94) of the patients in the SPA-negative group died, as compared with 10.3 percent (3 of 29) in the SPA-intermediate group and 34.6 percent (9 of 26) in the SPA-positive group. As compared with the SPA-negative group, the SPA-intermediate group had a relative risk of death of 1.6 (95 percent confidence interval, 0.5 to 5.5) and the SPA-positive group had a risk of 5.4 (95 percent confidence interval, 2.2 to 13.4). At least one cardiac event (cardiac death or recurrent nonfatal myocardial infarction) occurred in 14.9 percent (14 of 94 patients) of the SPA-negative group, 24.1 percent (7 of 29) of the SPA-intermediate group, and 46.2 percent (12 of 26) of the SPA-positive group. A positive test result continued to have prognostic value throughout the five-year study. We conclude that spontaneous platelet aggregation in vitro is a useful biologic marker for the prediction of coronary events and mortality in this low-risk group of survivors of a myocardial infarction. A causal relation is suggested but not proved by our study.New England Journal of Medicine 06/1990; 322(22):1549-54. · 51.66 Impact Factor
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ABSTRACT: An altered interaction between circulating LDL and endothelial cells might be at the basis of the increased prevalence of atherosclerosis in diabetes mellitus. The aim of the present work was to investigate the effect of a short incubation period with LDL from Type 1 diabetic patients in good metabolic control on endothelial cells derived from human aorta (HAEC). Cultured HAEC were incubated for 3 h with culture medium alone (control HAEC), with native LDL from healthy subjects (control LDL), or with native LDL from Type 1 diabetic patients (Type 1 LDL). After the incubation the following parameters were evaluated: endothelial cell nitric oxide synthase (NOS) activity, nitric oxide (NO) and peroxynitrite production, Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities, intracellular Ca(2+) concentration and fluidity of the superficial part of the plasma membrane studied by 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). Moreover, we studied the cellular activation, evaluated by the fluid phase endocytosis of TMA-DPH, and the microetherogeneity of the membrane surface, evaluated by dynamic fluorescence. HAEC incubated with control LDL showed compared with control HAEC: increased anisotropy and exponential lifetime of TMA-DPH, and enhanced TMA-DPH internalization. HAEC incubated with Type 1 LDL showed compared with both control HAEC and HAEC incubated with control LDL: (i) increased Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities, and intracellular Ca(2+) concentration; (ii) increased NOS activity, NO and peroxynitrite production; (iii) increased anisotropy of TMA-DPH; (iv) enhanced internalization of the probe. The exponential lifetime and the width of distribution of TMA-DPH were significantly increased by Type 1 LDL only in comparison with control HAEC. The results suggest that a short-term interaction with LDL from Type 1 diabetic patients causes alterations of the plasma membrane surface and of cellular functions in endothelial cells in a possibly atherogenic way.Atherosclerosis 12/2002; 165(1):69-77. · 3.71 Impact Factor