Update on vascular endothelial Ca²⁺signalling: A tale of ion channels, pumps and transporters

Abstract

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca 2+ signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca 2+ levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca 2+ signals, ranging from brief, localized Ca 2+ pulses to prolonged Ca 2+ oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca 2+ signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca 2+ releasing channels, which are located both on the plasma membrane and in a number of intracellular organelles, and Ca 2+ removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca 2+ machinery in vascular ECs under both physiological and pathological conditions.

VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2–dependent Ca 2+ signaling

“…Stimulation of ECs with VEGF is known to enhance production of IP 3 and elevate [Ca 2+ ] i (9). To characterize the possible contribution of each subtype of VEGFR to Ca 2+ signaling, primary cultures of HUVECs were stimulated with different concentrations of various VEGFR agonists ( Fig.…”

“…Stimulation of different EC types via VEGFR2 results in increases in intracellular free calcium concentrations [Ca 2+ ] i (9,10) and the crucial role of this signaling element in the regulation of EC functions and angiogenesis is recognized (11,12), and thought to be largely mediated by the phospholipase Cγ (PLCγ)/inositol 1,4,5 trisphosphate (IP 3 ) signaling pathway (10). It has been reported that IP 3 releases Ca 2+ from intracellular stores in ECs, increasing [Ca 2+ ] i , and is augmented by store-operated Ca 2+ influx (13).…”

Dysregulation of VEGF-induced proangiogenic Ca2+ oscillations in primary myelofibrosis-derived endothelial colony-forming cells

“…3B). PLCg cleaves the minor phospholipid component of the plasma membrane, phosphatidylinositol 4,5-biphosphate (PIP 2 ), into InsP 3 and DAG [32]. We thus focused on the role of InsP 3 -dependent Ca 2þ release in the onset of the Ca 2þ transients.…”

Mg(2+),ATP-dependent plasma membrane calcium pump of smooth muscle cells. ІІ. Regulation of activity

“…] c , та контролює гомео-стаз Са 2+ у клітині [84]. Окрім того, контроль Са 2+ -помпи ПМ здійснюється через G-протеїн паратиреоїдним гормоном, вазопресином та глюкагоном [66].…”