Abcg1

oxLDL

Macrophage

ABCA1 and apoA-I

Figure 4 An illustrated model of high-density lipoprotein (HDL) particle assembly and its role in reverse cholesterol transport (RCT). The process of collecting excess peripheral cholesterol by HDL for disposal via the liver is called the RCT pathway. HDL plays a key role in removing cholesterol from peripheral tissue. Lipid-free apolipoprotein AI (apoA-I) is secreted into the general circulation from the liver. ApoA-I accepts free cholesterol (FC) from cellular sites in the periphery including endothelial cells and macrophages by receptor-mediated processes including adenosine triphosphate-binding cassette (ABC) transporters, primarily ABCA1. Intermediate discoidal pre-b-HDLforms as the small, helical apoA-I accumulates phospholipid (PL) and free cholesterol (FC) which is further esterified to cholesteryl ester (CE) following the action of lecithyl cholesterol acyl transferase (LCAT). The pre-b-HDL particles also accept more FC from ABCA1 and develop further into spherical HDL2 and HDL3 particles, following the action of LCAT Spherical HDL2 and HDL3 particles and mature HDL do not interact well with ABCA1, but can access additional FC through apo-AI-mediated interaction with related specific macrophage ABCG1 transporters or the SR-B1 scavenger receptors found in peripheral cells. Intact spherical HDL2 and HDL3 particles and mature HDL can deliver FC and CE directly to the liver by a similar apo-AI-mediated interaction with the hepatic SR-B1 receptor. Alternatively, CE is transferred from HDL to LDL or VLDL following the action of cholesteryl ester transfer protein (CETP) and hepatic uptake of these apo-B particles removes excess cholesteryl esters via the LDL receptor. (Reprinted with permission by Keith Kasnot.)

superoxide anion) and reactive nitrogen species (RNS, e.g., nitric oxide, peroxynitrite) that alter the surrounding redox environment and stimulate the expression and secretion of several proinflammatory proteins that produce an elevated inflammatory response.

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