Abstract
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-alpha-induced monolayer permeability of human coronary artery endothelial cells (HCAECs). Cells were pretreated with STC1 for 30 minutes followed by treatment with TNF-alpha (2 ng/mL) for 24 hours. Monolayer permeability was studied using a transwell system. STC1 pretreatment significantly blocked TNF-alpha-induced monolayer permeability in a concentration- and time-dependent manner. STC1 effectively blocked TNF-alpha-induced downregulation of endothelial tight junction proteins zonula occluden-1 and claudin-1 at both mRNA and protein levels. STC1 also significantly decreased TNF-alpha-induced superoxide anion production. The inhibitory effect of STC1 was specific to TNF-alpha, as it failed to inhibit VEGF-induced endothelial permeability. Furthermore, STC1 partially blocked NF-kappaB and JNK activation in TNF-alpha-treated endothelial cells. JNK inhibitor and antioxidant also effectively blocked TNF-alpha-induced NF-kappaB activation and monolayer permeability in HCAECs. STC1 maintains endothelial permeability in TNF-alpha-treated HCAECs through preservation of tight junction protein expression, suppression of superoxide anion production, and inhibition of the activation of NFkappaB and JNK, suggesting an important role for STC1 in regulating endothelial functions during cardiovascular inflammation.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Arteriosclerosis, Thrombosis, and Vascular Biology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
