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Endothelial Ca2+ Signaling, Angiogenesis and Vasculogenesis: Just What It Takes to Make a Blood Vessel

1
Laboratory of General Physiology, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, 27100 Pavia, Italy
2
Research Centre, Salahaddin University-Erbil, Erbil 44001, Iraq
3
Department of Pathological Analysis, College of Science, Knowledge University, Erbil 074016, Iraq
4
Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, 86100 Campobasso, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 3962; https://doi.org/10.3390/ijms20163962
Received: 22 July 2019 / Revised: 9 August 2019 / Accepted: 13 August 2019 / Published: 14 August 2019
(This article belongs to the Special Issue Calcium Signaling in Human Health and Diseases 2.0)
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Abstract

It has long been known that endothelial Ca2+ signals drive angiogenesis by recruiting multiple Ca2+-sensitive decoders in response to pro-angiogenic cues, such as vascular endothelial growth factor, basic fibroblast growth factor, stromal derived factor-1α and angiopoietins. Recently, it was shown that intracellular Ca2+ signaling also drives vasculogenesis by stimulation proliferation, tube formation and neovessel formation in endothelial progenitor cells. Herein, we survey how growth factors, chemokines and angiogenic modulators use endothelial Ca2+ signaling to regulate angiogenesis and vasculogenesis. The endothelial Ca2+ response to pro-angiogenic cues may adopt different waveforms, ranging from Ca2+ transients or biphasic Ca2+ signals to repetitive Ca2+ oscillations, and is mainly driven by endogenous Ca2+ release through inositol-1,4,5-trisphosphate receptors and by store-operated Ca2+ entry through Orai1 channels. Lysosomal Ca2+ release through nicotinic acid adenine dinucleotide phosphate-gated two-pore channels is, however, emerging as a crucial pro-angiogenic pathway, which sustains intracellular Ca2+ mobilization. Understanding how endothelial Ca2+ signaling regulates angiogenesis and vasculogenesis could shed light on alternative strategies to induce therapeutic angiogenesis or interfere with the aberrant vascularization featuring cancer and intraocular disorders. View Full-Text
Keywords: endothelial cells; endothelial colony forming cells; vascular endothelial growth factor; basic fibroblast growth factor; stromal derived factor-1α; inositol-1,4,5-trisphosphate; store-operated Ca2+ entry; nicotinic acid adenine dinucleotide phosphate; TRPC channels endothelial cells; endothelial colony forming cells; vascular endothelial growth factor; basic fibroblast growth factor; stromal derived factor-1α; inositol-1,4,5-trisphosphate; store-operated Ca2+ entry; nicotinic acid adenine dinucleotide phosphate; TRPC channels
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Moccia, F.; Negri, S.; Shekha, M.; Faris, P.; Guerra, G. Endothelial Ca2+ Signaling, Angiogenesis and Vasculogenesis: Just What It Takes to Make a Blood Vessel. Int. J. Mol. Sci. 2019, 20, 3962.

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