Immunocytochemical analysis of connexin expression in the healthy and diseased cardiovascular system

Gap junctions play essential roles in the normal function of the heart and arteries, mediating the spread of the electrical impulse that stimulates sy nchronized contraction of the cardiac chambers, and contributing to co-ordi nation of activities between cells of the arterial wall. In common with oth er multicellular systems, cardiovascular tissues express multiple connexin isotypes that confer distinctive channel properties. This review highlights how state-of-the-art immunocytochemical and cellular imaging techniques, a s part of a multidisciplinary approach in gap junction research, have advan ced our understanding of connexin diversity in cardiovascular cell function in health and disease. In the heart, spatially defined patterns of express ion of three connexin isotypes-connexin43, connexin40, and connexin45-under lie the precisely orchestrated patterns of current flow governing the norma l cardiac rhythm. Derangement of gap junction organization and/or reduced e xpression of connexin43 are associated with arrhythmic tendency in the dise ased human ventricle, and high levels of connexin40 in the atrium are assoc iated with increased risk of developing atrial fibrillation after coronary by-pass surgery. In the major arteries, endothelial gap junctions may simul taneously express three connexin isotypes, connexin40, connexin37, and conn exin43; underlying medial smooth muscle, by contrast, predominantly express es connexin43, with connexin45 additionally expressed at restricted sites. In normal arterial smooth muscle, the abundance of connexin43 gap junctions varies according to vascular site, and shows an inverse relationship with desmin expression and positive correlation with the quantity of extracellul ar matrix. Increased connexin43 expression between smooth muscle cells is c losely linked to phenotypic transformation in early human coronary atherosc lerosis and in the response of the arterial wall to injury. Current evidenc e thus suggests that gap junctions in both their guises, as pathways for ce ll-to-cell signaling in the vessel wall and as pathways for impulse conduct ion in the heart, contribute to the initial pathogenesis and eventual clini cal manifestation of human cardiovascular disease. Microsc. Res. Tech. 52:3 01-322, 2001. (C) 2001 Wiley-Liss. Inc.