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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:2049.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

Involvement of Native TRPC3 Proteins in ATP-Dependent Expression of VCAM-1 and Monocyte Adherence in Coronary Artery Endothelial Cells

Kathryn Smedlund; Guillermo Vazquez

From the Department of Physiology and Pharmacology and the Center for Diabetes and Endocrine Research at the University of Toledo College of Medicine, Health Science Campus, Ohio.

Correspondence to Guillermo, Vazquez, Department of Physiology and Pharmacology, UTHSC Mail stop 1008, Toledo OH 43614. E-mail Guillermo.Vazquez{at}utoledo.edu

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 Ca²⁺ signaling. We here examined the role of Ca²⁺ influx and native TRPC3 channels in that mechanism.

Methods and Results— Omission of extracellular Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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.

We examined the role of Ca²⁺ influx and native TRPC3 proteins in regulated expression of VCAM-1 in coronary artery endothelial cells. The evidence shows that TRPC3 forms Ca²⁺-permeable channels whose expression and function are fundamental to VCAM-1 expression and monocyte adhesion, suggesting a potential pathophysiological role of TRPC3 in atherogenesis.

Key Words: TRPC3 • VCAM-1 • monocyte recruitment • Ca²⁺ influx • atherogenesis

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