The role of myoendothelial gap junctions in the formation of arterial aneurysms: the hypothesis of "connexin 43:40 stoichiometry".
Heterocellular myoendothelial gap junctions (MEGJs) are essential in coordinating and regulating vasomotion. Little is known about their potential role in disease states. We discuss how alteration in the Cx 43:40 expression ratio at the level of MEGJs may begin a chain of reactions in the arterial wall resulting in an aneurysm formation. In this model, we assumed that aneurysm is a chronic arterial disease associated with medial degeneration and intimal hyperplasia. It also was assumed that MEGJs are composed of Cx43 and Cx40 in different stoichiometry and that the characteristic of a given junction is in the favor of its most abundantly expressed constituent. The hypothesis of Cx 43:40 stoichiometry indicates that impaired MEGJs may play a role in the pathogenesis of arterial aneurysms. Cx43 upregulation and Cx40 downregulation (increased Cx 43:40 stoichiometry) may induce a cascade of inflammatory, electrical, metabolic and proliferative derangements in the arterial wall, which finally lead to the matrix degradation, intimal hyperplasia, endothelial-medial dissociation and loss of endothelium-dependent hyperpolarizing currents, irregular vasomotion, impaired growth factor activation, and arterial sympathetic deprivation. The final consequence of these alterations is aneurysm formation.
Shoja
Mohammadali M
MM
Tuberculosis and Lung Diseases Research Center, Tabriz Medical University, Tabriz, Iran. amohadjel@yahoo.com
Tubbs
R Shane
RS
Ansarin
Khalil
K
D000783:Aneurysm / Q000473:pathology; D000818:Animals; D049109:Cell Proliferation; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D017629:Gap Junctions; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D000097003:Gap Junction alpha-5 Protein
D018031:Connexin 43; D017630:Connexins; D036341:Intercellular Signaling Peptides and Proteins; D000097003:Gap Junction alpha-5 Protein