Abstract 489: Dual Role of Connexin37 in the Control of Vascular Inflammation and Smooth Muscle Cell Proliferation During Intimal Hyperplasia in Mice

Abstract

Introduction: The long term patency of vascular interventions is plagued by restenosis due to intimal hyperplasia (IH). Intercellular communication mediated by gap junctions plays a key role in tissue homeostasis and we recently showed that the gap junction protein Connexin43 (Cx43) contributes to smooth muscle cell (SMC) proliferation and IH. We now hypothesized that vascular Cx37 also plays a role in vascular remodeling and IH. Methods and Results: WT and Cx37 deficient mice (Cx37-/-) were subjected to the carotid artery ligation model. In WT mice, the ligation resulted in IH formation, as evidence by the development of a SMC -rich neointima after two to four weeks. This remodeling correlated with a reduced Cx37 expression in the endothelium layer and an increased Cx37 expression in the media layer. Compared to WT mice, Cx37-/- mice displayed a delayed development of neointima due to reduced infiltration of CD45-positive immune cells. However, Cx37-/- mice displayed an accelerated SMC proliferation rate between two and four weeks post surgery, as evidence by the number of PCNA-positive cells. Cx37-/- mouse arteries overexpressed synthetic SMC markers. Finally, in primary human vein SMC, Cx37 overexpression reduced cell proliferation and migration. Conclusions: Cx37 plays a dual role in neointima formation following vascular injury. Cx37 promotes immune cell infiltration and inflammation in the vessel. On the other hand, Cx37 overexpression in SMC counteracts the proliferative role of Cx43. Thus, Cx37 may play both protective and harmful roles in IH.