Endothelial remodelling and intracellular calcium machinery.
Rather being an inert barrier between vessel lumen and surrounding tissues, vascular endothelium plays a key role in the maintenance of cardiovascular homeostasis. The de-endothelialization of blood vessels is regarded as the early event that results in the onset of severe vascular disorders, including atherosclerosis, acute myocardial infarction, brain stroke, and aortic aneurysm. Restoration of the endothelial lining may be accomplished by the activation of neighbouring endothelial cells (ECs) freed by contact inhibition and by circulating endothelial progenitor cells (EPCs). Intracellular Ca(2+) signalling is essential to promote wound healing: however, the molecular underpinnings of the Ca(2+) response to injury are yet to be fully elucidated. Similarly, the components of the Ca(2+) toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the role of Ca(2+) signalling in endothelial repair and in EPC activation. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca(2+) channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca(2+) channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store-operated Ca(2+) entry (SOCE) stand amid the most proper routes to therapeutically induce the regrowth of denuded vessels. Cx stimulation might trigger the proliferative and migratory behaviour of ECs facing the lesion site, whereas activation of SOCE is likely to favour EPC homing to the wounded vessel.
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Moccia
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Tanzi
Laboratory of Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via Forlanini 6, 27100, Pavia, Italy. francesco.moccia@unipv.it.
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Munaron
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D017630:Connexins / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D055595:Mechanical Phenomena; D012038:Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D017630:Connexins; D002118:Calcium