Endothelial cell calcium entry pathways

Endothelial cell calcium entry pathways represent a complex network of channels and sensors that regulate the influx of Ca2+ into the vascular endothelium, a process vital for vascular homeostasis. The primary mechanism is store-operated calcium entry (SOCE), which involves the endoplasmic reticulum Ca2+ sensor STIM1 and the plasma membrane channel ORAI1 [1, 8]. Additionally, various Transient Receptor Potential (TRP) channels, such as TRPV4 and TRPC families, contribute to calcium entry in response to mechanical forces and chemical ligands [2, 5]. These pathways are essential for the activation of endothelial nitric oxide synthase (eNOS), which promotes vasodilation and maintains the endothelial barrier [4, 7]. Dysregulation of these pathways is implicated in diseases such as pulmonary arterial hypertension, where excessive calcium entry promotes endothelial-to-mesenchymal transition, and cancer, where it drives pathological angiogenesis [9, 11]. Therapeutic strategies include the use of small-molecule inhibitors like BTP2 for SOCE or specific TRP channel modulators to restore vascular function [10, 11]. However, the ubiquitous nature of calcium signaling poses challenges for achieving tissue-specific effects without systemic toxicity. Recent advances have identified novel mediators like EB3 that can be targeted to resolve pathological calcium signaling in acute lung injury [10].

Other names

Endothelial calcium signalingStore-operated calcium entry (SOCE)Receptor-operated calcium entry (ROCE)Endothelial Ca2+ influx

Modulation of calcium influx through store-operated (SOCE), receptor-operated (ROCE), and mechanosensitive channels to regulate endothelial function and vascular tone [1, 11].