The role of myoendothelial gap junctions in the formation of arterial aneurysms: The hypothesis of "connexin 43:40 stoichiometry"

Mohammadali Mohajel Shoja, R. Shane Tubbs, Khalil Ansarin

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)575-579
Number of pages5
JournalMedical Hypotheses
Volume69
Issue number3
DOIs
StatePublished - Jul 13 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Developmental Biology
  • Medicine(all)
  • Drug Discovery

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