Lipoproteins and lipid metabolism: lipoprotein metabolism. stable isotope kinetic study of apolipoprotein m in healthy subjects

Lipoproteins and lipid metabolism: lipoprotein metabolism. stable isotope kinetic study of apolipoprotein m in healthy subjects. Congress of the European-Atherosclerosis-Society (EAS

Carotid and femoral atherosclerotic plaques show different morphology

International audienceOBJECTIVE: Results of endovascular repair vary according to the arterial bed. We hypothesized that these differences may be related to the plaque features. To explore this hypothesis, we designed a prospective study that compared carotid and femoral atheroma. METHODS AND RESULTS: Patients that underwent femoral or carotid endarterectomy were included in our study. Demographic data and blood sampling were obtained prior to surgery. Plaques were evaluated for AHA grading, calcification and lipid content. Eighty-eight plaques were harvested during this study (45 carotid specimens and 43 femoral specimens). No differences were noted between carotid and femoral groups regarding demographic and biological data. Histological data more frequently showed fibrous cap atheroma in carotid arteries (75%) and fibrocalcific plaques in femoral arteries (93%), p<0.001. Morphological analyses showed a high prevalence of osteoid metaplasia in femoral arteries (63%) compared to carotid arteries (20%, p<0.001). Biochemical analyses were consistent with histological data, showing higher calcium and lesser cholesterol concentrations in femoral than in carotid plaques (p<0.01). CONCLUSIONS: Femoral and carotid plaques showed different morphology in comparable groups of patients

Nicotinic acid effects on insulin sensitivity and hepatic lipid metabolism: an in vivo to in vitro study

International audienceOur aim was to characterize the effects and the underlying mechanisms of the lipid-regulating agent Niaspan((R)) on both insulin action and triglyceride decrease in 20 nondiabetic, dyslipidemic men with metabolic syndrome receiving Niaspan((R)) (2 g/day) or placebo for 8 weeks in a randomized, cross-over study. The effects on plasma lipid profile were characterized at the beginning and the end of each treatment period; insulin sensitivity was assessed using the 2-step euglycemic hyperinsulinemic clamp and VLDL-triglyceride turnover by measuring plasma glycerol enrichment, both at the end of each treatment period. The mechanism of action of nicotinic acid was studied in HuH7 and mouse primary hepatocytes. Lipid profile was improved after Niaspan((R)) treatment with a significant-28% decrease in triglyceride levels, a+17% increase in HDL-C concentration and unchanged levels of fasting nonesterified fatty acid. VLDL-tri-glyceride production rate was markedly reduced after Niaspan((R)) (-68%). However, the treatment induced hepatic insulin resistance, as assessed by reduced inhibition of endogenous glucose production by insulin (0.7+/-0.4 vs. 1.0+/-0.5 mg/kg . min, p\textless0.05) and decrease in fasting hepatic insulin sensitivity index (4.8+/-1.8 vs. 3.2+/-1.6, p\textless0.05) in the Niaspan((R)) condition. Nicotinic acid also reduced insulin action in HuH7 and primary hepatocytes, independently of the activation of hepatic PKCepsilon. This effect was associated with an increase in diacylglycerol and a decrease in tri-glyceride contents that occurred in the absence of modification of DGAT2 expression and activity. Eight weeks of Niaspan((R)) treatment in dyslipidemic patients with metabolic syndrome induce hepatic insulin resistance. The mechanism could involve an accumulation of diacylglycerol and an alteration of insulin signaling in hepatocytes

Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo

Uptake of cholesterol from peripheral cells by nascent small HDL circulating in plasma is necessary to prevent atherosclerosis. This process, termed reverse cholesterol transport, produces larger cholesterol-rich HDL that transfers its cholesterol to the liver facilitating excretion. Most HDL in plasma is cholesterol-rich. We demonstrate that treating plasma with a novel selective delipidation procedure converts large to small HDL [HDL-selectively delipidated (HDL-sdl)]. HDL-sdl contains several cholesterol-depleted species resembling small α, preβ-1, and other preβ forms. Selective delipidation markedly increases efficacy of plasma to stimulate ABCA1-mediated cholesterol transfer from monocytic cells to HDL. Plasma from African Green monkeys underwent selective HDL delipidation. The delipidated plasma was reinfused into five monkeys. Preβ-1-like HDL had a plasma residence time of 8 ± 6 h and was converted entirely to large α-HDL having residence times of 13–14 h. Small α-HDL was converted entirely to large α-HDL. These findings suggest that selective HDL delipidation activates reverse cholesterol transport, in vivo and in vitro. Treatment with delipidated plasma tended to reduce diet-induced aortic atherosclerosis in monkeys measured by intravascular ultrasound. These findings link the conversion of small to large HDL, in vivo, to improvement in atherosclerosis