Coronary endothelium expresses a pathologic gene pattern compared to aortic endothelium: Correlation of asynchronous hemodynamics and pathology in vivo

Abstract

Coronary arteries are the most disease prone arteries in the circulation and are characterized by unique hemodynamic features, wherein wall shear stress (WSS) induced by blood flow and circumferential strain (CS) driven by pressure are highly out-of-phase temporally (asynchronous hemodynamics). To investigate whether there is a correlation between asynchronous hemodynamics and pathology in vivo, we examined endothelial cell (EC) gene expression and nuclear morphology in two distinct hemodynamic regions of male New Zealand rabbits: coronary arteries (left anterior descending artery cLAD), and aorta (aortic arch inner curvature, outer curvature, and straight descending aorta). En face imaging showed strong similarities in EC nuclear length:width ratio and angle of orientation in the cLAD and aorta. Real-time RT-PCR, however, showed that coronary arteries had significantly reduced (>5-fold) eNOS mRNA levels compared to all aortic regions, while ET-1 showed an opposite trend (∼2.5-fold). Coronary arteries with characteristic asynchronous hemodynamics displayed pro-atherogenic eNOS and ET-1 gene expression profiles while the EC nuclei morphology did not differ from non-atherogenic regions in the aorta. This study demonstrates a correlation between asynchronous hemodynamics and pro-atherogenic gene expression patterns in vivo that is induced by hemodynamics inherent to the circulation.