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

  • Ion channels, receptors and transporters
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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.

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Sources of funding

This work was supported by the NIH (HL095566 to KM and HL097111 to MT), AHA grants (14GRNT18880008 to MT and 16850060 to MK), and Applied Biophysics Inc. Troy, NY to JS.

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None.

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Authors and Affiliations

  1. Department of Physiological Sciences, EVMS, Norfolk, VA, 23501, USA

    Modar Kassan, Karima Ait Aissa & Khalid Matrougui

  2. Nanobioscience Constellation, College of Nanoscale Science and Engineering, SUNY, Albany, NY, 12203, USA

    Wei Zhang, Judith Stolwijk & Mohamed Trebak

Authors
  1. Modar Kassan
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  2. Wei Zhang
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  3. Karima Ait Aissa
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  4. Judith Stolwijk
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  5. Mohamed Trebak
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  6. Khalid Matrougui
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Corresponding author

Correspondence to Khalid Matrougui.

Additional information

Modar Kassan and Wei Zhang have equally contributed to this work.

Khalid Matrougui and Mohamed Trebak share senior authorship.

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Kassan, M., Zhang, W., Aissa, K.A. et al. Differential role for stromal interacting molecule 1 in the regulation of vascular function. Pflugers Arch - Eur J Physiol 467, 1195–1202 (2015). https://doi.org/10.1007/s00424-014-1556-5

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  • DOI: https://doi.org/10.1007/s00424-014-1556-5

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