"Vascular remodeling: functional consequences of altered connexin expression"

ABSTRACT
Connexin (Cx) expression in the endothelial and medial layers of the vessel wall changes duringdevelopment and as a consequence of injury and disease. The mechanistic basis for, and functional consequences of, altered Cx expression in the vessel wall remain uncertain.

To explore these issues we have implemented a coarctation model that results in localized hemodynamic changes without inducing disease, vascular injury, or systemic hemodynamic effects. The abdominal aortas of 3-6 month old adult mice were surgically coarcted, distal to the renal arteries, using a U-shaped clip (0.2 mm gap). Within the clipped region, which encompasses ~1.5 mm of vessel length, the vessel assumes a rectangular cross-section (~200 um x 900 um, O.D. with rounded ends) wherein wall strain is reduced but shear stress increased. Carotid artery blood pressure was not affected by clip placement (n=2) and was unchanged (n=1) 8 days later when the vessel was harvested for further study. Coarctation-induced remodeling of the vessel wall included increased expression of Cx43 within, and at the boundaries of, the clipped region in the endothelium, as well as reorientation of the endothelial cells up-and downstream of the coarcted region.

The impact of these coarctation-induced changes in vascular Cx expression on cell-cell coupling and junctional selectivity is being explored using a dual dye injection technique; wherein two fluorescent dyes of similar size but opposite charge are introduced to the same cell in the endothelial layer of a live aorta,and their spread throughout the monolayer quantified. It is anticipated that the selectivity of intercellular communication in the endothelial layer will change from cation selective, reflecting high Cx37 and Cx40 expression, to a more non-selective profile as Cx43 expression increases.