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Differential role for stromal interacting molecule 1 in the regulation of vascular function
Journal article   Peer reviewed

Differential role for stromal interacting molecule 1 in the regulation of vascular function

Modar Kassan, Wei Zhang, Karima Ait Aissa, Judith Stolwijk, Mohamed Trebak and Khalid Matrougui
Pflügers Archiv, Vol.467(6), pp.1195-1202
2015
DOI: 10.1007/s00424-014-1556-5
PMCID: PMC4843990
PMID: 24965067
url
https://www.ncbi.nlm.nih.gov/pmc/articles/4843990View
Open Access

Abstract

We determined the in vivo role of stromal-interacting molecule 1 (STIM1) in the regulation of vascular function using endothelial cell (EC)- and smooth-muscle (SM)-specific knockout mice. Systolic blood pressure and glucose levels were similar in all mice (Stim1 SMC−/− , Stim1 SMC−/+ , Stim1 EC−/− , Stim1 EC−/+ ), but body weight was reduced in Stim1 EC−/− and Stim1 SMC−/− mice. The contraction of arteries in response to phenylephrine was significantly reduced in Stim1 SMC−/− mice only. However, contraction to thromboxane and KCl was similar in all groups. The endothelium-dependent relaxation (EDR) was impaired in Stim1 EC−/+ and drastically reduced in Stim1 EC−/− mice while the endothelium-independent vasorelaxation was similar among all groups. Acute downregulation of STIM1 in arteries reduced EDR and the contractile response to phenylephrine, while the contractile response to thromboxane was not affected. NADPH oxidase activity was increased only in Stim1 EC−/+ and Stim1 EC−/− mice. Calcium (Ca 2+ ) entry in endothelial cells stimulated with thrombin and histamine had the pharmacological features of store-operated Ca 2+ entry (SOCE) and was dependent on STIM1 expression. We conclude that STIM1 plays opposing roles in vascular smooth muscle vs. endothelial cells in the regulation of vascular reactivity.
Biomedical and Life Sciences Biomedicine Cell Biology Human Physiology Ion Channels Molecular Medicine Neurosciences Receptors Receptors and Transporters

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