Multiple Connexin Expression in Regenerating Arterial Endothelial Gap Junctions

Abstract

Abstract-Endothelial cells form gap junctions that, according to vessel type, may be composed of up to 3 types of connexin, connexin37, connexin40, and connexin43. Although changes in connexin expression have been linked to growth and injury in cultured endothelial cells, information on connexin expression in regenerating endothelium in situ is lacking. We investigated gap junction distribution and expression of all 3 endothelial connexins during healing in rat carotid artery after denudation injury. En face viewing of the vascular luminal surface by means of immunoconfocal microscopy was used to examine the spatial and temporal expression pattern of the endothelial connexins. Gap junction spots labeled by specific antisera against connexin37, connexin40, and connexin43 were quantified 7, 14, and 28 days after injury, and the relations among the connexins were examined by using colocalization analysis. Complementary electron microscopy was also conducted. After injury, the regenerating endothelium initially expressed small, sparse gap junctions, the numbers of which progressively increased to values equivalent to those of controls. Although connexin40 gap-junctional spot size and area returned to uninjured levels by 28 days after injury, connexin37 and connexin43 spot size and area exceeded those of the uninjured artery (PϽ0.05). Double-label analysis showed that even though colocalization of connexins to the same gap-junctional spot is a common feature, the extent of colocalization was time dependent (Ͼ80% in the intact artery at postinjury day 28 and Ͻ70% at postinjury days 7 and 14, PϽ0.01). We conclude that distinct alterations in expression of the 3 connexins are associated with regeneration of the arterial endothelium in situ, implying different intercellular communication requirements during the various phases of the healing process.

Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

“…Moreover, a critical role for Cx43 has been reported in human saphenous vein during the development of intimal hyperplasia (Deglise et al 2005) and restenosis (Plenz et al 2004) and Cx43 decreases smooth muscle cell proliferation and limits neointima formation after vascular injury (Chadjichristos et al 2006). Conversely, regeneration of the endothelium following carotid artery injury in rats, a process essential for wound healing, is associated with increasing expression of Cx37, Cx40, and Cx43 (Yeh et al 2000). More detailed investigations of the significance of altered connexin expression is required before any clear consensus on the role of gap junction expression in mediating the beneficial effect of estrogens in vessel repair can be made.…”

Association of candidate gene polymorphisms with bone mineral density in community-dwelling Japanese women and men

“…Gap junction protein, ·-4 (connexin37) is a gap junction protein in the arterial endothelium and contributes to the growth and regeneration after injury of endothelial cells (25). It forms functional intercellular channels with a voltage dependence and unitary conductance properties that are distinct from those of other channels (26).…”

Downregulation of Connexin 43 Expression by High Glucose Reduces Gap Junction Activity in Microvascular Endothelial Cells

“…Although there is considerable information on expression of Cx37, Cx40, and Cx43 in endothelial cells from large vessels of bovine, rat (17,18), pig (13), and human (19), little is known about connexin expression or GJIC activity in microvascular endothelial cells. In this study, we investigated the effect of high glucose concentrations on GJIC activity in microvascular endothelial cells and determined whether changes in GJIC activity are associated with connexin gene expression.…”