Reverse cholesterol transport pathway in experimental chronic renal failure.

Abstract

BACKGROUND Chronic renal failure (CRF) causes oxidative stress, inflammation, oxidation of lipoproteins, impaired maturation of HDL and accelerated atherosclerosis. Uptake of oxidized lipoproteins by macrophages via scavenger receptors (scavenger receptor class A type I--SR-AI, and lectin-like oxidized LDL receptor--LOX-1) leads to foam cell formation and atherosclerosis. HDL mitigates atherosclerosis by retrieving surplus cholesterol via ATP binding cassette transporter A1 (ABCA1) and ABCG1 transporters whose expression is regulated by liver X receptor (LXR). Free cholesterol reaching the surface of HDL is esterified by lecithin-cholesterol acyltransferase (LCAT) and sequestered in the core of HDL, thereby maximizing cholesterol uptake. In the liver, lipid-rich HDL unloads its lipid contents via reversible binding to SR-BI while lipid-poor HDL is degraded by the holo-receptor (ATP synthase beta-chain). METHODS Expression of the above molecules involved in reverse cholesterol/lipid transport was assessed in rats 8 weeks after 5/6 nephrectomy (CRF) or sham operation. RESULTS CRF caused heavy accumulation of neutral lipids, upregulation of SR-AI, LOX-1, LXRalpha/beta, ABCA1 and ABCG1 in the aorta, reduction in LCAT in the plasma and no significant change in either SR-BI or beta-chain ATP synthase in the liver. CONCLUSIONS Lipid accumulation despite upregulation of the efflux (LXR, ABCA1, ABCG1) system in the aorta in CRF is largely due to upregulation of influx (SR-AI and LOX-1) pathway and LCAT deficiency.

DOI: 10.1159/000210020

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@article{Moradi2009ReverseCT, title={Reverse cholesterol transport pathway in experimental chronic renal failure.}, author={Hamid Moradi and Jun Yuan and Zhemin Ni and Keith C. Norris and Nosratola D. Vaziri}, journal={American journal of nephrology}, year={2009}, volume={30 2}, pages={147-54} }