Apolipoprotein A-II is a key regulatory factor of HDL metabolism as appears from studies with transgenic animals and clinical outcomes

Abstract

The structure and metabolism of HDL are linked to their major apolipoproteins (apo) A-I and A-II. HDL metabolism is very dynamic and depends on the constant remodeling by lipases, lipid transfer proteins and receptors. HDL exert several cardioprotective effects, through their antioxidant and antiinflammatory capacities and through the stimulation of reverse cholesterol transport from extrahepatic tissues to the liver for excretion into bile. HDL also serve as plasma reservoir for C and E apolipoproteins, as transport vehicles for a great variety of proteins, and may have more physiological functions than previously recognized. In this review we will develop several aspects of HDL metabolism with emphasis on the structure/function of apo A-I and apo A-II. An important contribution to our understanding of the respective roles of apo A-I and apo A-II comes from studies using transgenic animal models that highlighted the stabilizatory role of apo A-II on HDL through inhibition of their remodeling by lipases. Clinical studies coupled with proteomic analyses revealed the presence of dysfunctional HDL in patients with cardiovascular disease. Beyond HDL cholesterol, a new notion is the functionality of HDL particles. In spite of abundant literature on HDL metabolic properties, a major question remains unanswered: which HDL particle(s) confer(s) protection against cardiovascular risk?

Keywords: ABCA1; ABCG1; ATP binding cassette transporter A1; ATP binding cassette transporter G1; Apo A-I; Apo A-II; Atherosclerosis; CE; CE transfer protein; CETP; CVD; EL; FA; FC; HDL; HL; HSPG; KO; LCAT; LPL; Lipases; MI; PAF-AH; PL; PL transfer protein; PLTP; PON1; RCT; SR-BI; TG; TG-rich lipoproteins; TICE; TRL; apo; apo B-LP; apo B-containing lipoproteins; apolipoprotein; cardiovascular diseases; cholesterol ester; d; density; endothelial lipase; fatty acid; free cholesterol; hapo A-I; hapo A-II; heparan sulfate proteoglycans; hepatic lipase; high density lipoproteins; human apo A-I; human apo A-II; knockout; lecithin-cholesterol-acyltransferase; lipoprotein lipase; mapo A-II; murine apo A-II; myocardial infarction; paraoxonase 1; phospholipid; platelet-activating factor acetylhydrolase; rHDL; reconstituted HDL; reverse cholesterol transport; scavenger receptor class B type I; transintestinal cholesterol excretion; triglyceride.