Connexins and intercellular communication in arterial growth and remodeling

Gap junction functionality and intercellular exchange of chemical messengers and other biologically important cellular signals makes communication between adjacent cells possible and is essential for multicellular living systems. This intercellular communication is carried out through gap junction channels that are comprised of multimeric connexin (Cx) proteins and that provide physical linkages between neighboring cells. This Cx-specific gap junction intercellular communication (GJIC) helps perform numerous essential physiological functions in different organ systems. In vascular tissues, reciprocal GJIC between intimal vascular endothelial cells (VECs) and medial vascular smooth muscle cells (VSMCs) helps to control blood flow and arterial pressures by signaling contraction or relaxation events. In the vascular system appropriate GJIC also regulates responses to circulating hormones and other vasoactive factors as well as growth during episodes of stimulated angiogenesis and/or vasculogenesis. Deleterious GJIC, however, serves as a contributing element in vascular pathologies and plays key roles in abnormal vascular cell proliferation, migration, and inflammation, foundational mechanisms of arterial remodeling and neointima development. In this review we discuss the critical roles of vascular gap junction Cx proteins and GJIC in regulating pathologic arterial remodeling.