Connexins: New genes in atherosclerosis

Atherosclerosis, the main cause of death and disability in adult populations of industrialized societies, is a multifactorial progressive process involving a variety of pathogenic mechanisms. Our current view on the pathogenesis of the disease implies complex patterns of interactions between a dysfunctional endothelium, leukocytes, and activated smooth muscle cells in which cytokines and growth factors are known to play a crucial role. Apart from paracrine cell-to-cell signalling, a role for gap junction-mediated intercellular communication in the development of the disease has been recently suggested. Gap junction channels result from the docking of two hemichannels or connexons, formed by the hexameric assembly of connexins, and directly connect the cytoplasm of adjacent cells. In this review, we summarize existing evidence implicating connexins in atherosclerosis. Indeed, the expression pattern of vascular connexins is altered during atherosclerotic plaque formation. In addition, changes in connexin expression or gap junctional communication have been observed in vascular cells in vitro by disturbances in blood flow, cholesterol, inflammatory cytokines, and growth factors. Furthermore, genetically modifying connexin expression affects the course of the atherosclerotic process in mouse models of the disease. Finally, the involvement of connexins in treatment of atherosclerotic disease will be discussed.