Low HDL and High HDL Syndromes

Plasma high-density lipoprotein cholesterol (HDL-C) level correlates negatively with the incidence of coronary heart disease (CHD). Low HDL syndrome, a condition in which plasma HDL-C is low, is a dyslipidemia frequently observed in patients with premature CHD. The antiatherogenic functions of HDL have been demonstrated by a number of experiments in vitro and in vivo. The injection of HDL and its major apolipoprotein (apo) constituent, apoA-I, was shown to attenuate atherosclerosis in animal models. Lipid-poor apoA-I and HDL remove cholesterol from lipid-laden foam cells via ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1), respectively. The cholesterol is esterified by lecithin: cholesterol acyltransferase (LCAT) to form cholesteryl ester (CE). The CE of HDL is transferred by plasma cholesteryl ester transfer protein (CETP) to very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) in exchange for triglycerides (TG). The TG in HDL is hydrolyzed by hepatic lipase (HL); thus, HDL becomes smaller to take up more cholesterol from foam cells. Furthermore, the IDL and LDL are taken up by hepatic LDL receptor. The CE of HDL particle is taken up by the liver via scavenger receptor class B type I (SR-BI). Thus, excess cholesterol in the foam cells of arteries is transported back to the liver, a process called “reverse cholesterol transport (RCT).” In the liver, cholesterol is catabolized into bile acid and excreted into the bile. The plasma levels of HDL-C as well as the biochemical composition and functions of HDL particles are regulated by apolipoproteins, lipolytic enzymes, lipid transfer proteins, receptors, and cellular transporters such as ABCA1 and ABCG1. Furthermore, transcription factors such as liver X receptor (LXR) and farnesoid X receptor (FXR) that regulate the expression of ABCA1 and ABCG1 are also involved in the regulation of plasma HDL-C levels.