Ca2+-dependent nitric oxide release in the injured endothelium of excised rat aorta: a promising mechanism applying in vascular prosthetic devices in aging patients

BMC Surgery

Research Article

José Everardo Avelino-Cruz¹  Francesco Moccia¹  Franco Tanzi¹  Alessandro Della Corte²  Germano Guerra³  Abdul Raqeeb⁴  Stefania Montagnani⁵  Mariapia Cinelli⁵  Roberto Berra-Romani⁶ 

[1] Department of Biology and Biotechnology "Lazzaro Spallanzani", Laboratory of Physiology, University of Pavia, via Forlanini 6, 27100, Pavia, Italy;Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy;Department of Medicine and Health Sciences, University of Molise, via F. De Sanctis, 86100, Campobasso, Italy;Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada;Department of Public Health, University of Naples "Federico II", via Pansini 5, 80131, Naples, Italy;School of Medicine, Department of Biomedicine, Benemérita Universidad Autónoma de Puebla, 13 Sur 2702, 72000, Colonia Volcanes, Puebla, Mexico;

关键词: Nitric Oxide;    Aortic Ring;    Decay Phase;    Wound Edge;    eNOS Activation;   

DOI  :  10.1186/1471-2482-13-S2-S40

来源: Springer

【 摘 要 】

BackgroundNitric oxide is key to endothelial regeneration, but it is still unknown whether endothelial cell (EC) loss results in an increase in NO levels at the wound edge. We have already shown that endothelial damage induces a long-lasting Ca2+ entry into surviving cells though connexin hemichannels (CxHcs) uncoupled from their counterparts on ruptured cells. The physiological outcome of injury-induced Ca2+ inflow is, however, unknown.MethodsIn this study, we sought to determine whether and how endothelial scraping induces NO production (NOP) in the endothelium of excised rat aorta by exploiting the NO-sensitive fluorochrome, DAF-FM diacetate and the Ca2+-sensitive fluorescent dye, Fura-2/AM.ResultsWe demonstrated that injury-induced NOP at the lesion site is prevented in presence of the endothelial NO synthase inhibitor, L-NAME, and in absence of extracellular Ca2+. Unlike ATP-dependent NO liberation, the NO response to injury is insensitive to BTP-2, which selectively blocks store-operated Ca2+ inflow. However, injury-induced NOP is significantly reduced by classic gap junction blockers, and by connexin mimetic peptides specifically targeting Cx37Hcs, Cx40HCs, and Cx43Hcs. Moreover, disruption of caveolar integrity prevents injury-elicited NO signaling, but not the accompanying Ca2+ response.ConclusionsThe data presented provide the first evidence that endothelial scraping stimulates NO synthesis at the wound edge, which might both exert an immediate anti-thrombotic and anti-inflammatory action and promote the subsequent re-endothelialization.

【 授权许可】

Unknown   
© Berra-Romani et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.