Coronary heart disease: Significance of liver X receptor alpha genomics

Crosstalk between lipid peroxidation and inflammation is known to be a pathognomonic feature for the development of coronary heart disease (CHD). In this regard ligand activated liver X receptor (LXR)-alpha has emerged as a key molecular switch by its inherent ability to modulate an array of genes involved in these two fundamental cellular processes. In addition, LXR-alpha has also been found to play a role in hepatic lipogenesis and innate immunity. Although several lines of evidence in experimental model systems have established the atheroprotective nature of LXR-alpha, human subjects have been reported to possess a paradoxical situation in which increased blood cellular LXR-alpha gene expression is always accompanied by increased coronary occlusion. This apparent paradox was resolved recently by the finding that CHD patients possess a deregulated LXR-alpha transcriptome due to impaired ligand-receptor interaction. This blood cellular mutated LXR- a gene expression correlated specifically with the extent of coronary occlusion and hence need is felt to devise new synthetic ligands that could restore the function of this mutated LXR-alpha protein in order to modulate genes involved in reverse cholesterol transport and suppression of the inflammatory response leading to the effective treatment of CHD. (C) 2010 Baishideng. All rights reserved.