Endothelial Remodelling and Intracellular Calcium Machinery

Abstract

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.

GABABReceptors Expressed in Human Aortic Endothelial Cells Mediate Intracellular Calcium Concentration Regulation and Endothelial Nitric Oxide Synthase Translocation

“…Intracellular Ca 2+ contributes to vascular endothelium physiology, functions, and disorders such as proliferation [14], apoptosis [15], permeability [16], endothelial nitric oxide synthase (eNOS) activation [17], injury [18], and healing [19]. Other neural-transmitter receptor types that are generally thought of as having primarily central neural system locations and functions have been shown to be present within the peripheral vascular endothelium cells and modify the intracellular Ca 2+ .…”

A Functional Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Is Expressed in Human Endothelial Progenitor Cells

“…Vascular endothelial cells line the lumen of blood and lymphatic thereby forming a multifunctional signal transduction platform that maintains cardiovascular homeostasis (Mancardi et al, ; Moccia et al, ). Endothelial injury is recognized as initial step in the onset of severe cardiovascular diseases, including myocardial infarction, brain stroke, atherosclerosis and diabetes (Moccia et al, ; Moccia et al, ).…”

A method for high-throughput functional imaging of single cells within heterogeneous cell preparations

“…The method introduced here is positioned to be useful in assessing the impact of cell-cell interactions on discrete cellular functions, a possibility that awaits additional study. Possible examples include interactions between regulatory and effector T cells within different target tissues51, stem cells whose differentiation may be effected by contact with other cell types52, and, in general, in cell types that are functionally coupled through gap junctions53. These are all instances that offer an opportunity for further exploration and application of our mode of analysis in future studies.…”