Jennifer S. Fang PhD Candidate Physiological Sciences GIDP Experimental Biology 2008 San Diego, California April 5-9, 2008 “Connexin37 Regulation of Vascular Remodeling Following Ischemic Injury” Jennifer S. Fang, Alexander M. Simon, Janis M. Burt

Gap junction proteins Connexin37 (Cx37) and Connexin40 (Cx40) are strongly expressed in normal endothelium, although their specific function(s) in this tissue are poorly understood. Previously, we have shown by dual-dye injection of oppositely-charged dyes that both Cx37 and Cx40 channels are similarly cation-selective. Despite similarities in permselectivity, expression of Cx37 – but not Cx40 – suppresses proliferation of otherwise connexin-deficient rat insulinoma cells, suggesting that Cx37 may be uniquely suited to regulating endothelial cell proliferation and turnover in vivo. Using the unilateral hindlimb ischemia model to induce a vascular remodeling response in wild-type and Cx37-deficient animals, we show that revascularization following induction of ischemia (as determined by comparison of vascular density in ischemic versus non-ischemic tissue) is enhanced in Cx37-deficient animals compared to wild-type controls. These findings are consistent with the hypothesis that in mature endothelium, Cx37 suppresses cell proliferation and prevents uncontrolled remodeling of the vasculature. Further, the inhibitory effect of Cx37 is temporarily relieved by downregulation of its expression during the revascularization response induced by ischemia. Supported by: AHA 550158Z (JMB), HL064232 (AMS) and AHA0715532Z (JSF).