Ca2+ Signalling in Damaged Endothelium: Do Connexin Hemichannels Aid in Filling the Gap?

Author(s): Francesco Moccia, Jose Everardo Avelino-Cruz, Yuly Sanchez-Hernandez, Franco Tanzi

Journal Name: Current Drug Therapy

Volume 5 , Issue 4 , 2010

Become EABM
Become Reviewer
Call for Editor


A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that regulates cardiovascular homeostasis. Disruption of endothelial integrity, as a result of either angioplasty or stent deployment, may produce a late in-stent restenosis and limit the beneficial outcome of reconstructive vascular surgery. Restoration of endothelial lining requires spreading, migration and proliferation of ECs nearby the lesion site. Intracellular Ca2+ signalling plays a major regulatory role in stimulating wound healing, however, the mechanism whereby injury increases Ca2+ levels at the wound edge is still unclear. The analysis of Ca2+ signals elicited by scraping an endothelial monolayer in vitro suggested the involvement of intracellular Ca2+ release from InsP3-sensitive stores and Ca2+ entry through unknown ion channels in the plasma membrane. Recent studies carried out by our group on excised rat aorta highlighted a novel role for connexin hemichannels (ChHcs) in mediating Ca2+ entry in injured endothelium. This observation sheds new light on the notion that the rate of wound repair is reduced in ECs transfected with dominant negative connexin inhibitors. Understanding the signal transduction pathway leading to EC activation is likely to provide novel targets to design therapeutic applications aiming at restoring endothelial integrity and treating cardiovascular diseases.

Keywords: Rat aorta, endothelial injury, connexin hemichannels, Ca2+ entry, cardiovascular disorders, drug eluting stents, Ca2+ signalling, cardiovascular homeostasis, fibrinolysis, angiogenesis, paracrine mediators, nitric oxide, endothelin-1, prostanoids, prostacyclins, restenosis, atherosclerotic disease, neointimal hyperplasia, in-stent restenosis, sirolimus, paclitaxel, G-protein coupled receptors, plasminogen activator, inositol-1,4,5-trisphosphate, heterotetramers, gap-junction inhibitor, heptanol, angioplasty, membrane-impermeable dyes, trypan blue, propidium iodide, rhodamine dextran, sub-membranal, cytosol, plasmalemmal channels, lamellipodium, m-calpain, proliferative band, ectonucleotidase activity, aliphatic alcohols, octanol, fatty acids, oleamide, palmitoleic acid, trivalent cation, apolipoprotein-E knockout, arrhythmia, atrial fibrillation, rotigaptide, fluvastatin, lovastatin, pravastatin, simvastatin, glutathione

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2010
Page: [277 - 287]
Pages: 11
DOI: 10.2174/157488510792927483
Price: $65

Article Metrics

PDF: 11