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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:906.)
© 2008 American Heart Association, Inc.

Cell Biology and Signaling

Human Stanniocalcin-1 Blocks TNF-–Induced Monolayer Permeability in Human Coronary Artery Endothelial Cells

Changyi Chen; Md Saha Jamaluddin; Shaoyu Yan; David Sheikh-Hamad; Qizhi Yao

From the Molecular Surgeon Research Center (C.C., M.S.J., S.Y., Q.Y.), Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery; and the Renal Section (D.S.-H.), Department of Medicine, Baylor College of Medicine, Houston, Tex.

Correspondence to Changyi (Johnny) Chen, MD, PhD, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Mail stop: NAB-2010, Houston, TX 77030. E-mail jchen{at}bcm.tmc.edu

Objective— Our previous studies revealed upregulation of stanniocalcin-1 (STC1) in cardiac vessels in dilated cardiomyopathy. However, the functional significance of STC1 is unknown. The objective of this study was to determine the effects of STC1 on TNF-–induced monolayer permeability of human coronary artery endothelial cells (HCAECs).

Methods and Results— Cells were pretreated with STC1 for 30 minutes followed by treatment with TNF- (2 ng/mL) for 24 hours. Monolayer permeability was studied using a transwell system. STC1 pretreatment significantly blocked TNF-–induced monolayer permeability in a concentration- and time-dependent manner. STC1 effectively blocked TNF-–induced downregulation of endothelial tight junction proteins zonula occluden-1 and claudin-1 at both mRNA and protein levels. STC1 also significantly decreased TNF-–induced superoxide anion production. The inhibitory effect of STC1 was specific to TNF-, as it failed to inhibit VEGF-induced endothelial permeability. Furthermore, STC1 partially blocked NF-B and JNK activation in TNF-–treated endothelial cells. JNK inhibitor and antioxidant also effectively blocked TNF-–induced NF-B activation and monolayer permeability in HCAECs.

Conclusions— STC1 maintains endothelial permeability in TNF-–treated HCAECs through preservation of tight junction protein expression, suppression of superoxide anion production, and inhibition of the activation of NFB and JNK, suggesting an important role for STC1 in regulating endothelial functions during cardiovascular inflammation.

Key Words: stanniocalcin-1 • TNF- • endothelial cell • permeability • superoxide anion

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