ABCA1 is upregulated in athero‐protected regions of arteries in response to brief hypercholesterolemia treatment in vivo

Abstract

Endothelial cells (EC) in atherosclerosis‐prone regions of arteries display distinct gene expression profiles compared to athero‐protected regions. We investigated the differential alteration of EC phenotype at these sites during brief hypercholesterolemia. Eleven adult male swine were fed a normal chow diet (n=6) or an isocaloric high fat diet (n=5) for a period of 2 weeks. EC RNA was isolated from 3 protected (carotid, descending thoracic, renal arteries) and 3 susceptible (aortic arch, renal branch, abdominal aorta) arterial regions, linearly amplified and hybridized to porcine microarrays. Fifty eight lipid metabolism related genes were differentially expressed in ECs from all regions in response to hypercholesterolemia. However, ATP Binding Cassette A1 (ABCA1), an endothelial transmembrane protein that regulates phospholipids and cholesterol homeostasis inside the cell in response to changing levels of cholesterol in the blood, was specifically upregulated in athero‐protected regions. This response was also validated at the protein level by immunohistochemistry. Region‐specific upregulation of ABCA1 transcript and protein in ECs demonstrates a site‐specific differential EC phenotypic response to hypercholesterolemia. Supported by grants from NHLBI.