Coronary heart disease: Significance of liver X receptor α 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)-α 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-α 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-α, human subjects have been reported to possess a paradoxical situation in which increased blood cellular LXR-α 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-α transcriptome due to impaired ligand-receptor interaction. This blood cellular mutated LXR-α 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-α protein in order to modulate genes involved in reverse cholesterol transport and suppression of the inflammatory response leading to the effective treatment of CHD.