Recent studies in man and human apolipoprotein A-I transgenic animals emphasize the significance of apolipoprotein A-I and high density lipoprotein in antiatherogenesis. Several drugs and other compounds, e.g. phenobarbital, gemfibrozil, fenofibrate, prednisone, estrogen and alcohol, induce apolipoprotein A-I synthesis. They commonly produce serum lipoprotein patterns typical of a low risk of coronary heart disease, and many of them have been found to prevent atherogenesis, reduce coronary heart disease mortality and increase survival.
Cholesterol-laden macrophages are the hallmark of atherogenesis. The class B scavenger receptor, CD36, binds oxidized low density lipoprotein (OxLDL), is found in atherosclerotic lesions, and is upregulated by OxLDL. We tested the effects of alpha-tocopherol (AT) enrichment of human monocyte-derived macrophages on CD36 expression and cholesteryl ester accumulation. Monocytes isolated from normal volunteers were cultured into macrophages. Macrophages were enriched overnight with various doses of AT (25, 50, and 100 microM).
ACAT2, the enzyme responsible for the formation of cholesteryl esters incorporated into apolipoprotein B-containing lipoproteins by the small intestine and liver, forms predominantly cholesteryl oleate from acyl-CoA and free cholesterol. The accumulation of cholesteryl oleate in plasma lipoproteins has been found to be predictive of atherosclerosis. Accordingly, a method was developed in which fatty acyl-CoA subspecies could be extracted from mouse liver and quantified.
Arteriosclerosis, Thrombosis, and Vascular Biology
OBJECTIVES: The enzyme acyl-coenzymeA (CoA):cholesterol O-acyltransferase 2 (ACAT2) in the liver synthesizes cholesteryl esters (CE) from cholesterol and fatty acyl-CoA, which get incorporated into apoB-containing lipoproteins that are secreted into the bloodstream. Dietary fatty acid composition influences the amount and fatty acid composition of CE within apoB-containing lipoproteins.
Arteriosclerosis, Thrombosis, and Vascular Biology
OBJECTIVE: The objective of this study was to determine the effects and potential mechanisms of C-reactive protein (CRP) on cholesterol efflux from human macrophage foam cells, which may play a critical role in atherogenesis. METHODS AND RESULTS: Human THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) were preincubated with acetylated LDL and [3H]-cholesterol to form foam cells, which were then treated with apolipoprotein A-I (apoA-I) or HDL for cholesterol efflux assay.
Human protein S is an anticoagulation protein. However, it is unknown whether protein S could regulate the expression and function of macrophage scavenger receptor A (SR-A) in macrophages. Human THP-1 monocytes and peripheral blood monocytes were differentiated into macrophages and then treated with physiological concentrations of human protein S. We found that protein S significantly reduced acetylated low-density lipoprotein (AcLDL) uptake and binding by macrophages and decreased the intracellular cholesteryl ester content.
This review focuses on the relationships among dietary fat type, plasma and liver lipid, and lipoprotein metabolism and atherosclerosis. Dietary polyunsaturated fatty acids are beneficial for the prevention of coronary artery atherosclerosis. By contrast, dietary monounsaturated fatty acids appear to alter hepatic lipoprotein metabolism, promote cholesteryl oleate accumulation, and confer atherogenic properties to lipoproteins as shown in data from experimental animal studies.
Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs.
The effects of acute caloric restriction on cholesterol balance and kinetics of plasma cholesterol specific activity were investigated in five hyperlipemic subjects with varying degrees of obesity. Caloric restriction decreased plasma triglycerides by 41 +/- 12%, plasma cholesterol by 11 +/- 9%, and the ratio of esterified to free cholesterol by 12 +/- 7+. Immediately on institution of caloric restriction there appeared to be an influx of tissue cholesterol into plasma and a reduction in endogenous synthesis of cholesterol.
The effects of a large dose (2 mg/100 g body weight) of medroxyprogesterone acetate (MPA), restricted feeding (50% of normal intake) and their interaction were investigated on the serum and liver lipid and protein distribution in female rats. MPA increased serum cholesterol and triglyceride levels in rats on ad libitum food intake without having any effect in the animals on restricted diet. There was no statistical difference in the total serum protein or albumin levels among the groups. The serum levels of alpha and gamma globulin were significantly lower in the underfed rats.