OBJECTIVE Low high-density lipoprotein (HDL) cholesterol levels are frequently observed in familial hypercholesterolemia (FH) and might be associated with functional alterations of HDL particles that may influence their efficaciousness in the reverse cholesterol transport pathway. METHODS AND RESULTS We evaluated key steps of the reverse cholesterol transport, ie, cellular free cholesterol ef...

OBJECTIVE To compare the abilities of human wild-type apoA-I (WT apoA-I) and human apoA-I(Milano) (apoA-I(M)) to promote macrophage reverse cholesterol transport (RCT) in apoA-I-null mice infected with adeno-associated virus (AAV) expressing either WT apoA-I or apoA-I(M). METHODS AND RESULTS WT apoA-I- or apoA-I(M)-expressing mice were intraperitoneally injected with [H(3)]cholesterol-labeled...

The concept of “reverse cholesterol transport” (RCT) was first introduced in 1968 by Glomset1 to describe the process by which extrahepatic (peripheral) cholesterol is returned to the liver for excretion in the bile and ultimately the feces. The physiological need for this process is clear, as nonhepatic cells acquire cholesterol through uptake of lipoproteins and de novo synthesis and yet (wit...

This study was aimed to investigate the effect of human PON1 overexpression in mice on cholesterol efflux and reverse cholesterol transport. PON1 overexpression in PON1-Tg mice induced a significant 3-fold (p<0.0001) increase in plasma paraoxonase activity and a significant ~30% (p<0.0001) increase in the capacity of HDL to mediate cholesterol efflux from J774 macrophages compared to wild-type ...

BACKGROUND Chronic renal failure (CRF) causes oxidative stress, inflammation, oxidation of lipoproteins, impaired maturation of HDL and accelerated atherosclerosis. Uptake of oxidized lipoproteins by macrophages via scavenger receptors (scavenger receptor class A type I--SR-AI, and lectin-like oxidized LDL receptor--LOX-1) leads to foam cell formation and atherosclerosis. HDL mitigates atherosc...

Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharm...

ABCA1 was recently identified as the mutant molecule in Tangier disease, a condition associated with very low HDL, cholesteryl ester accumulation in tissue macrophages, and an apparent increased risk of atherosclerotic cardiovascular disease. ABCA1 is an ATP-binding cassette transporter that facilitates the addition of phospholipids and cholesterol to free apoA-I, initiating the formation of HD...

Cholesterol efflux (ChE) from macrophages is an initial step of reverse cholesterol transport (RCT). The ATP-binding cassette transporter A1 (ABCA1) is a key transporter for ChE and its increased expression is regarded to attenuate atherosclerosis. Thus, the identification and characterization of molecules raising ABCA1 and thereby stimulating ChE is of pharmacological relevance. In this study,...

Statins, inhibitors of the key enzyme in the biosynthesis of cholesterol (ie, 3-hydroxy-3-methylglutaryl [HMG]coenzyme A [CoA] reductase), are widely used as the prevailing strategy to combat atherosclerosis through reducing LDL cholesterol levels. Large-scale clinical trials have shown that statins markedly reduce coronary events.1,2 A meta-analysis of 22 studies enrolling nearly 70 000 indivi...