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Editorial
. 2014 Sep;34(9):1800-2.
doi: 10.1161/ATVBAHA.114.304156.

Reconstituted high-density lipoprotein therapies: a cause for optimism

Ali Javaheri  1 , Daniel M Kolansky  1 , Marina Cuchel  2
Affiliations
Editorial

Reconstituted high-density lipoprotein therapies: a cause for optimism

Ali Javaheri et al. Arterioscler Thromb Vasc Biol. 2014 Sep.
No abstract available

Keywords: ATP-binding cassette transporter 1; CSL112; acute coronary syndrome.

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Figures

Figure 1
Figure 1
Panel A. Reverse cholesterol transport. ApoA-I (synthesized in the liver and intestines) acquires phospholipid and a small amount of free cholesterol via the ABCA1 transporter to form nascent Preβ-HDL. Preβ-HDL is the preferred acceptor of cholesterol effluxed by ABCA1 and acquires additional lipids from peripheral cells such as macrophages in the arterial wall. LCAT esterifies free cholesterol to hydrophobic cholesteryl esters, which migrate into the HDL core, driving the maturation of HDL into spherical α particles. Mature HDL particles are able to acquire additional lipids via other pathways, such as those mediated by ABCG1 or SR-BI, or by a passive diffusion process. Cholesterol carried on HDL can be delivered directly to the liver via SR-BI. Alternatively, cholesteryl ester present on HDL can be exchanged for triglycerides by CETP and transferred to VLDL and LDL, and delivered to the liver via the LDL-receptor. Once in the liver, cholesterol can be excreted with the bile, either as free cholesterol or after being converted to a bile salt. Panel B. HDL remodeling. HDL is constantly remodeled in the circulation by numerous enzymes and proteins. Nascent pre-β HDL acquires free cholesterol by ABCA1. HDL-free cholesterol is esterified by LCAT, to form mature HDL that can acquire more cholesterol. Mature HDL particles can unload their lipid cargo by several mechanism: via CETP that transfer cholesteryl ester to apoB-containing lipoproteins; via endothelial lipase (EL) and hepatic lipases (HL) that can hydrolyze phospholipid and triglycerides respectively; via liver SR-BI, that can selectively uptake cholesterol. Through the loss of apoA-I and other proteins, HDL particles lose volume, regenerating lipid poor, nascent pre-βHDL. Insufficiently lipidated apoA-I is catabolized by the kidney. Infusion of reconstituted HDL is associated with increased production of nascent, pre-β HDL, possibly favoring HDL remodeling and decreasing renal catabolism.
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