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Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):2049-55. doi: 10.1161/ATVBAHA.108.175356. Epub 2008 Sep 11.

Involvement of native TRPC3 proteins in ATP-dependent expression of VCAM-1 and monocyte adherence in coronary artery endothelial cells.

Author information

1
Department of Physiology and Pharmacology, Center for Diabetes and Endocrine Research, University of Toledo College of Medicine, Health Science Campus, Ohio 43614, USA.

Abstract

Background- Vascular cell adhesion molecule-1 (VCAM-1) is critical in monocyte recruitment to the endothelium, a key event in development of atherosclerotic lesions. Stimulation of human coronary artery endothelial cells (HCAECs) with ATP positively modulates VCAM-1 expression and function through a mechanism involving Ca(2+) signaling. We here examined the role of Ca(2+) influx and native TRPC3 channels in that mechanism.

METHODS AND RESULTS:

Omission of extracellular Ca(2+) or pretreatment of cells with channel blockers markedly reduced ATP-induced VCAM-1 and monocyte adhesion. Using a siRNA strategy and real-time fluorescence, we found that native TRPC3 proteins contribute to constitutive and ATP-regulated Ca(2+) influx. ATP-dependent upregulation of VCAM-1 was accompanied by an increase in basal cation entry and TRPC3 expression. Notably, TRPC3 knock-down resulted in a dramatic reduction of ATP-induced VCAM-1 and monocyte adhesion.

CONCLUSIONS:

These findings indicate that in HCAECs, native TRPC3 proteins form channels that contribute to constitutive and ATP-dependent Ca(2+) influx, and that TRPC3 expression and function are fundamental to support VCAM-1 expression and monocyte binding. This is the first evidence to date relating native TRPC3 proteins with regulated expression of cell adhesion molecules in coronary endothelium, and suggests a potential pathophysiological role of TRPC3 in coronary artery disease.

PMID:
18787184
DOI:
10.1161/ATVBAHA.108.175356
[Indexed for MEDLINE]

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