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.

• Authors: Hamid Moradi, Jun Yuan, Zhemin Ni, Keith Norris, Nosratola D Vaziri
• Journal: American journal of nephrology (Am J Nephrol) Vol. 30 Issue 2 Pg. 147-54 ( 2009) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 19321994 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright 2009 S. Karger AG, Basel.

Chemical References

• Lipids
• Receptors, Scavenger
• Cholesterol

Topics

• Animals
• Cholesterol (metabolism)
• Gene Expression Regulation
• Inflammation
• Kidney Failure, Chronic (blood)
• Lipids (chemistry)
• Liver (metabolism)
• Macrophages (metabolism)
• Male
• Models, Biological
• Nephrectomy
• Oxidative Stress
• Rats
• Rats, Sprague-Dawley
• Receptors, Scavenger (metabolism)