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Atherosclerosis is a multi-factorial inflammatory disease of the vessel wall of medium- to large-sized arteries. The disease is characterised by specific lesions in the intimal layer of arteries (called atheromas), where the traditional components of a chronic inflammatory response such as the extravasation and accumulation of leukocytes, presence of necrotic debris, deposition of extracellular matrix and apparition of angiogenesis, can all be found. When the stability of an atheroma is compromised, i.e. when the balance between the fibrous elements and inflammatory components is lost, the lesion can rupture, resulting in thrombus formation and obstruction of the diseased artery.
Epidemiological studies have indicated that a polymorphism in the human connexin37 (Cx37) gene may serve as a prognostic marker for atherosclerosis. Connexins are integral membrane proteins that oligomerize to form intercellular channels called gap junctions. Cx37 is mostly expressed in endothelial cells, monocytes and macrophages. Studies on genetically-modified mouse models have demonstrated that Cx37 is generally atheroprotective. Expression of Cx37 by monocytes inhibits their adhesion and thus reduces initiation of atherosclerosis. Moreover, Cx37 expression in the arterial endothelium is induced by high laminar shear stress (HLSS) and involves the transcription factor KLF-2. Shear stress-induced regulation of Cx37 expression creates endothelial communication compartments, which may contribute to localisation of disease.
In this presentation, I will discuss the role of Cx37 in atherosclerosis and provide a potential mechanism by which the C1019T polymorphism in the Cx37 gene protects against myocardial infarction and stroke.
Brenda R. Kwak, PhD
Dept. of Pathology and Immunology
Dept. of Internal Medicine – Cardiology
University of Geneva Medical School