Vascular Connexins in Pathologic Conditions

Vascular endothelium has the capacity to form gap junctions with circulating cells such as neutrophils expressing Cx43 and macrophages expressing Cx37. Such interactions may be significant in the development of inflammation, particularly since inflammation increases Cx43 expression in endothelial cells and leukocytes [12]. In contrast, myoen-dothelial cell-cell communication is downregulated in inflammation. The gap-junctional role in inflammation is also indicated in that gap junction inhibitors promote vascular leak and transvascular cell migration [13], suggesting that gap junctions help maintain vascular barrier function. Tumor cell extravasation might also be regulated by gap-junctional communication, since melanoma cells expressing high levels of Cx26 are able to communicate with vascular endothelium and are more metastatic than cells that lack connexin expression. Interestingly, since Cx26 is believed to be incompatible with Cx37, Cx40, and Cx43, the melanoma cell-endothelial interaction may be attributable to a novel mode of gap-junctional communication, or to an unknown endothelial connexin that pairs with Cx26.

Gap-junctional communication between foam cells and the vascular wall is also likely to promote atherosclerotic plaque formation [14]. Consistent with a role for Cx43 in plaque formation, Cx43 +/- deficient mice that are deficient for LDL receptor expression show significantly less endothelial Cx43 expression and fewer atherosclerotic plaques than mice expressing normal levels of Cx43. Cx43 upregulation in response to disturbed flow during plaque formation or in response to vessel injury may exacerbate this effect. Whether other connexins are involved in plaque formation remains to be determined; however, there are some hints that Cx37 may also play such a role. One possibility is that while some gap-junctional communication is important for transvascular cell migration, excessive cell-cell coupling can be inhibitory, which, in turn, could stabilize a foam cell precursor at sites of plaque formation.

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Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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