Prediction of Coronary Conduit Artery Endothelial Cell Phenotype by Phenotypic Assessment in the Systemic Vasculature

Abstract

Human studies have established a correlation between endothelial vasomotor function assessed at the brachial and coronary arteries. This relationship spurred widespread investigation of brachial artery vasomotor function and, more recently, the isolation and phenotypic analysis of endothelial cells harvested invasively from the brachial artery (presumably with the application of understanding the coronary vascular endothelium). However, notwithstanding the correlation between vasomotor function in brachial and coronary arteries, the degree to which markers of endothelial cell phenotype correlate between systemic and coronary arteries is unknown. PURPOSE: Determine the degree to which endothelial cell phenotype assessed in peripheral conduit vessels is predictive of phenotype in the coronary artery endothelium in swine. METHODS: Isolated segments of thoracic and abdominal aorta, carotid, brachial, femoral, renal, internal mammary, and right coronary arteries were harvested at the time of sacrifice from 19 swine. Vessels were placed in a dissection buffer, cleaned of excess connective tissue, cut longitudinally, and the endothelium was mechanically scraped yielding an endothelial enriched sample of vascular cells. Samples were subsequently probed for eNOS, HSP90, p67phox, SOD1 and SOD3 protein expression via immunobloting. RESULTS: Expression of eNOS, HSP90, SOD1, and SOD3 was on average well correlated (p < 0.05 vs. coronary artery for each vessel) between systemic conduit arteries and the right coronary artery (mean rho value = 0.71 ± 0.02, 0.83 ± 0.02, 0.72 ± 0.02, and 0.91 ± 0.01 for eNOS, HSP90, SOD1, and SOD3, respectively). In contrast, expression of p67phox in systemic conduit artery endothelium was not correlated to that in the right coronary artery (mean rho value = 0.24 ± 0.04, p > 0.05 vs. coronary artery for each vessel). CONCLUSION: We conclude that endothelial cell protein expression assessed in peripheral conduit arteries is predictive of expression levels in the conduit coronary arteries in the cases of some (e.g., eNOS, HSP90, SOD1 and SOD3) but not all (e.g., p67phox) markers of endothelial cell phenotype. Supported by: P01-HL052490 (M.H.L.) and T32-AR048523 (G.H.S. and J.P.).