Abstract 220: Shear Stress Induces the Expression of Connexin-43 in Human Coronary Smooth Muscle
Coronary collaterals normally do not accommodate blood flow unless an upstream occlusion diverts blood flow through them. This blood flow provides an initiating stimulus, shear stress on the vessel wall, to increase collateral vessel diameter and wall thickness. This process, termed arteriogenesis, requires chemoattraction of monocytes into the vessel wall and vascular smooth muscle proliferation. Therefore, communication of the shear signal from the endothelium to the underlying smooth muscle is necessary. Previously, we demonstrated that endothelial cells exposed to shear stress release hydrogen peroxide which signals the underlying smooth muscle to express the arteriogenic factor, placenta growth factor (PLGF). Additional signaling pathways are involved in arteriogenesis although the mechanisms of communication across the vessel wall and regulation are still largely unknown. Connexins (Cx) are transmembrane proteins that form hemichannels between cells which enable direct exchange of signaling molecules. Vascular connexins have been shown to modulate blood flow, angiogenesis, and are correlated with atherosclerosis; however, very little is known of their role in arteriogenesis, particularly in human coronary vasculature. In this study, human coronary artery endothelial cells (CAEC) were co-cultured on membranes with coronary artery smooth muscle cells (CASMC) to mimic the vessel wall structure. We hypothesized that co-cultures exposed to high shear stress would exhibit an altered expression pattern of vascular connexins relative to static and normal shear stress. We show that 2 h of high shear stress at the endothelial surface significantly increases (3 fold) the expression of Cx43 in coronary smooth muscle while Cx37 and Cx40 are undetectable under static and shear conditions. Shear stress did not drive a significant change in the expression of Cx37, Cx40, or Cx43 in coronary endothelial cells compared to static conditions. Taken together with our previously published work, the data suggest that expression of Cx43 by human coronary smooth muscle may play a role in shear signaling pathways for arteriogenesis.
- © 2013 by American Heart Association, Inc.