Abstract
Ca2+ handling plays an important role in endothelial functions including regulation of vascular tone. An increase of intracellular [Ca2+] triggers the production of vasodilatative factors in endothelial cells (ECs) and leads to vascular relaxation. The [Ca2+] in the endoplasmic reticulum (ER) determines in great part the generation of important Ca2+ signals, and many proteins contribute to ER Ca2+ refilling after store depletion, most notably, stromal interaction molecule 1/2 (STIM1/2), Orai1/2/3, and sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase 3 (SERCA3) in ECs. Although endothelial dysfunction has been implicated in the diabetic heart, little is known about the contribution of STIM1. Vascular relaxation induced by ACh in coronary arteries (CAs) from diabetic mice was significantly attenuated compared with control CAs. Mouse coronary ECs (MCECs) isolated from diabetic mice exhibited a significant decrease in CPA‐induced Ca2+ release from the ER and had significantly lower protein expression levels of STIM1 than control. Furthermore, STIM1 positive mutant overexpression restored the Ca2+ release from ER in diabetic mice. These data suggest that impaired ER Ca2+ refilling due to downregulation of STIM1 protein expression attenuates CA relaxation in diabetes and leads to diabetic coronary vascular disease. This research was supported by grant DK083506.
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 callDisclaimer: 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.
