Table 4.

Role of the I_CRAC in endothelial dysfunction.

Endothelial Cell Type	Evidence of ICRAC Involvement	Function	Reference
HUVECs	siOrai1, Orai1over	ICAM-1 and VCAM-1 expression, monocyte adhesion	[177]
Mouse aorta and lungs	Orai1over	Expression of ICAM-1 and VCAM-1 and of pro-inflammatory cytokines (IL-6, IL-8, MCP-1 and E-selectin) in the aorta, lung inflammation	[177]
HUVECs	siSTIM1, siOrai1	LPS-induced apoptosis	[185,186]
mPAECs	STIM1EC-/- mice, BTP-2 (1 mg/kg for in vivo experiments; 5 µM BTP-2 for in vitro experiments)	LPS-induced leukocyte infiltration, increase in pro-inflammatory cytokines, endothelial cell death, vascular leakage and pulmonary edema	[178]
hPMECs	BTP-2 (1 mg/kg for in vivo experiments; 20 µM BTP-2 for in vitro experiments)	Cyclic stretching-induced increase in endothelial permeability Ventilation-induced increase in pulmonary permeability	[183]
EA.hy926	siSTIM1, siOrai1, 1–20 µM SKF-96365 and 50–70 µM 2-APB	HMGB1-increase in permeability	[181]
HUVECs	siOrai1	von Willebrand factor release	[22]

Abbreviations: ALI: acute lung injury; hPMECs: human pulmonary microvascular endothelial cells; HMGB1: High-mobility group box 1 protein; HUVECs: human umbilical vein endothelial cells; LPS: lipopolysaccharide; mPAECs: mouse pulmonary artery endothelial cells; rPMECs: rat pulmonary microvascular endothelial cells; siOrai1: small interfering RNA selectively targeting Orai1; siSTIM1: small interfering RNA selectively targeting STIM1; STIM1^EC-/- mice: endothelial cell-specific knockout mice; STIM1^over: STIM1 overexpression.