HDL biogenesis and functions: Role of HDL quality and quantity in atherosclerosis

Abstract 

Coronary heart disease (CHD) is a leading cause of death in western societies. In the last few decades, a number of epidemiological studies have shown that a disproportion between atheroprotective and atherogenic lipoproteins in plasma is one of the most important contributors towards atherosclerosis and CHD. Thus, based on the classical view, reduced HDL cholesterol levels independently predict one's risk factor for developing cardiovascular disease, while elevated HDL levels protect from atherosclerosis. However, more recent studies have suggested that the relationship between HDL and cardiovascular risk is more complex and extends beyond the levels of HDL in plasma. These studies challenge the existing view on HDL and cardiovascular risk and trigger a discussion as to whether low HDL is a causal effect for the development of heart disease. In this article we provide a review of the current literature on the biogenesis of HDL and its proposed functions in atheroprotection. In addition, we discuss the significance of both HDL quality and quantity in assessing cardiovascular risk.

Abbreviations: CHD, coronary heart disease, LDL, low density lipoprotein, LDLr, low density lipoprotein receptor, apoA-I, apolipoprotein A-I, apoE, apolipoprotein E, apoCIII, apolipoprotein CIII, HDL, high density lipoprotein, VLDL, very low density lipoprotein, SR-BI, scavenger receptor class B type I, ABCA1, ATP-binding cassette A1, CETP, cholesteryl-ester transfer protein, LCAT, lecithin:cholesterol acyl transferase, MCP-1, monocyte chemotactic protein-1, CCR2, CC chemokine receptor 2, SRA I, scavenger receptor I, SRA II, scavenger receptor II, CD36, cluster of differentiation 36, LpL, lipoprotein lipase, HL, hepatic lipase, EL, endothelial lipase, PLTP, phospholipid transfer protein, RCT, reverse cholesterol transport, HPODE, hydroperoxyoctadecadieonic acid, HPETE, hydroperoxyeicosatetraenoic acid, PON, paraoxonase, PAFAH, platelet activating factor acetylhydrolase, eNOS, endothelial nitric oxide synthase, CRP, C-reactive protein, TGFβ2, transforming growth factor β2

Keywords: Apolipoprotein AI, Apolipoprotein CIII, Apolipoprotein E, Atherosclerosis, Anti-atherogenic functions, High density lipoprotein, HDL biogenesis, HDL functions, HDL quantity, HDL quality