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

Modar Kassan, Wei Zhang, Karima Ait Aissa, Judith Stolwijk, Mohamed Trebak, Khalid Matrougui

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 (Stim1SMC−/−, Stim1SMC−/+, Stim1EC−/−, Stim1EC−/+), but body weight was reduced in Stim1EC−/− and Stim1SMC−/− mice. The contraction of arteries in response to phenylephrine was significantly reduced in Stim1SMC−/− mice only. However, contraction to thromboxane and KCl was similar in all groups. The endothelium-dependent relaxation (EDR) was impaired in Stim1EC−/+ and drastically reduced in Stim1EC−/− 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 Stim1EC−/+ and Stim1EC−/− mice. Calcium (Ca2+) entry in endothelial cells stimulated with thrombin and histamine had the pharmacological features of store-operated Ca2+ 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.

Original languageEnglish (US)
Article number4
Pages (from-to)1195-1202
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume467
Issue number6
DOIs
StatePublished - Jun 23 2015

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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