Calcium Mobilization in Endothelial Cell Functions

Abstract

Endothelial cells (ECs) constitute the innermost layer that lines all blood vessels from the larger arteries and veins to the smallest capillaries, including the lymphatic vessels. Despite the histological classification of endothelium of a simple epithelium and its homogeneous morphological appearance throughout the vascular system, ECs, instead, are extremely heterogeneous both structurally and functionally. The different arrangement of cell junctions between ECs and the local organization of the basal membrane generate different type of endothelium with different permeability features and functions. Continuous, fenestrated and discontinuous endothelia are distributed based on the specific function carried out by the organs. It is thought that a large number ECs functions and their responses to extracellular cues depend on changes in intracellular concentrations of calcium ion ([Ca2+]i). The extremely complex calcium machinery includes plasma membrane bound channels as well as intracellular receptors distributed in distinct cytosolic compartments that act jointly to maintain a physiological [Ca2+]i, which is crucial for triggering many cellular mechanisms. Here, we first survey the overall notions related to intracellular Ca2+ mobilization and later highlight the involvement of this second messenger in crucial ECs functions with the aim at stimulating further investigation that link Ca2+ mobilization to ECs in health and disease.

SARAF and Orai1 Contribute to Endothelial Cell Activation and Angiogenesis

“…The process of angiogenesis is tightly regulated by pro-angiogenic factors such as VEGF which binds to its receptors on ECs and mediates [Ca 2+ ] i increase ( Munaron et al, 2008 ). The close relationship between EC physiology and Ca 2+ signaling has been extensively studied ( Filippini et al, 2019 ). Nevertheless, only few studies reported the role of SOCE in angiogenesis.…”

Role of Junctional Adhesion Molecule-C in the Regulation of Inner Endothelial Blood-Retinal Barrier Function

“…As an essential second messenger of endothelial cells, calcium plays a critical role in regulating barrier function and inflammation. And increased cytosolic Ca 2+ levels can induce tight junction disassembly, increased permeability ( Filippini et al, 2019 ; Dalal et al, 2020 ), and angiogenesis ( Wong and Yao, 2011 ). VEGF has been shown to induce cytosolic Ca 2+ elevation in retinal endothelial cells ( Hiroishi et al, 2007 ).…”

Caveolae and Lipid Rafts in Endothelium: Valuable Organelles for Multiple Functions

“…Whilst closely located to the highest available oxygen supply, i.e., the bloodstream, ECs prefer to rely on the less efficient aerobic glycolysis (the conversion of glucose into lactate instead of pyruvate) [ 123 ] rather than on oxidative phosphorylation (OXPHOS) for energy production [ 124 ]. It has been estimated that the number of mitochondria in the endothelium is considerably low with respect to other cell types, and in ECs, these organelles appear mainly involved in the regulation of cellular processes such as Ca 2+ homeostasis, redox signaling, and cell death and only marginally contribute to EC energy needs [ 125 , 126 ]. By a mere energetic point of view, though the choice of ECs for the aerobic metabolism appears less advantageous with respect to the OXPHOS, it is functionally successful.…”