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. 1998 Mar 1;101(5):1064–1075. doi: 10.1172/JCI445

Native low density lipoprotein-induced calcium transients trigger VCAM-1 and E-selectin expression in cultured human vascular endothelial cells.

S Allen 1, S Khan 1, F Al-Mohanna 1, P Batten 1, M Yacoub 1
PMCID: PMC508658  PMID: 9486977

Abstract

Low density lipoprotein (LDL) interactions with the endothelium are thought to play a major role in the development of atherosclerosis. The mechanism(s) involved are not fully understood, although several lines of evidence support the idea that oxidation of LDL increases its atherogenicity. In this study we report for the first time that native LDL (n-LDL) binding to the LDL receptor (100-700 mug/ml) triggers a rise in intracellular calcium which acts as a second messenger to induce vascular cell adhesion molecule-1 (VCAM-1) expression in human coronary artery (HCAEC) and pig aortic endothelial cells (PAEC) and VCAM-1 and E-selectin expression in human aortic (HAEC) endothelial cells. Preincubation of HCAEC with a monoclonal antibody (IgGC7) to the classical LDL receptor or pretreatment with pertussis toxin blocked the n-LDL-induced calcium transients. Preincubation of each of the endothelial cell lines with the calcium chelator 1,-2-bis(o-aminophenoxy)ethane-N,N,N', N'-tetraacetic acetomethyl ester (BAPTA/AM) prevented the expression of VCAM-1 and E-selectin. The increase in VCAM-1 by n-LDL results in increased monocyte binding to HCAEC which can be attenuated by inhibiting the intracellular calcium rise or by blocking the VCAM-1 binding sites. These studies in human and pig endothelial cells link calcium signaling conferred by n-LDL to mechanisms controlling the expression of endothelial cell adhesion molecules involved in atherogenesis.

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Selected References

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