Endothelial Remodelling and Intracellular Calcium Machinery.

The endothelium is not merely a semi-permeable barrier between circulating blood and surrounding tissues, but it 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, such as atherosclerosis, myocardial infarction, 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 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. Similarly, the components of the Ca2+ toolkit that drive EPC incorporation into denuded vessels are far from being fully elucidated. The present review will survey the current knowledge on the molecular mechanisms shaping the Ca2+ response to endothelial injury and driving EPC proliferation and incorporation into blood vessels. We propose that endothelial regeneration might be boosted by intraluminal release of specific Ca2+ channel agonists or by gene transfer strategies aiming to enhance the expression of the most suitable Ca2+ channels at the wound site. In this view, connexin (Cx) channels/hemichannels and store-operated Ca2+ 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