Genomic changes caused by chronic exposure to high cholesterol or fish oil in native and regenerated porcine coronary endothelial cells

Abstract

The genomic changes associated with endothelial lesions caused by balloon angioplasty and hypercholesterolemia or those affected by dietary fish oil in porcine coronary arteries were analyzed using large scale microarray gene expression profiling. Pigs were fed with high cholesterol (CHL) diet or fish oil diet rich in omega-3 unsaturated fatty acids. Arterial endothelial denudation was performed by percutaneous transluminal coronary angioplasty of the left anterior descending artery (LAD). Cells from left circumflex (native cells) and LAD (regenerated cells) were harvested for primary culture and subsequent genomic microarray experiments four weeks after the surgery. The plasma levels of LDL-C, triglycerides and arachidonic acid were elevated while those of HDL-C were reduced in the CHL group. Fish oil treatment reduced the plasma levels of arachidonic acid, LDL-C, HDL-C, and the LDL-C/HDL-C ratio. Only 27 genes showed differential regulations, whereas 385 genes were altered similarly by hypercholesterolemia and regeneration. In addition, hypercholesterolemia induced 396 gene changes that were independent of endothelial regeneration. Fish oil significantly reduced the number of gene changes associated with regeneration (176 genes). Regeneration-induced changes of 72 genes were either completely or partially blocked by fish oil. Thus, the present study identifies endothelial genomic changes associated with both hypercholesterolemia-induced prelesional responses and postlesional damage caused by regeneration. The genes responsible for the potential protective effects of fish oil were determined.