Abstract
Differential role for STIM1 in the regulation of vascular function (851.7)
The FASEB journal, Vol.28(S1), pp.851.7-n/a
04/2014
DOI: 10.1096/fasebj.28.1_supplement.851.7
Abstract
Background: The aim of this study was to determine the role of stromal interacting molecule‐1 (STIM1) in the regulation of vascular function using tissue‐specific STIM1 knockout mice either in endothelial cells or in smooth muscle cells.
Methods & results: We used male C57/BL6 homozygous and heterozygous mice lacking STIM1 specifically in either smooth muscle cells (STIM1SMC‐/‐, STIM1SMC‐/+) or in endothelial cells (STIM1EC‐/‐, STIM1EC‐/+). Systolic blood pressure and glucose levels were similar in all mice, but body weight was significantly reduced in STIM1EC‐/‐ and STIM1SMC‐/‐ mice. The contraction of resistance and conductance arteries in response to phenylephrine was significantly reduced in STIM1SMC‐/‐ mice only. However, contraction to thromboxane and potassium chloride was similar in all groups. The endothelium‐dependent relaxation was significantly impaired in STIMEC‐/+ and drastically reduced in STIM1EC‐/‐ mice while the endothelium‐independent vasorelaxation was similar among all groups. Acute down regulation of STIM1 in resistance arteries reduced endothelium‐dependent relaxation to acetylcholine and the contractile response to phenylephrine, while the contractile response to thromboxane was not affected. NADPH oxidase activity was only increased in STIMEC‐/+ and STIMEC‐/‐ mice. Calcium Ca2+ entry in microvascular endothelial cells stimulated with thrombin and histamine, two vasoactive compounds that cause NO production, had the pharmacological features of store‐operated Ca2+ entry (SOCE) and was dependent on STIM1 expression.
Conclusions: STIM1 plays opposing roles in vascular smooth muscle vs. endothelial cells in the regulation of vascular reactivity. We conclude that STIM1 is a critical factor in the basic mechanisms of vascular endothelium‐dependent relaxation and the contractility in response to sympathetic activity but not in the intrinsic contractility of smooth muscle.
Details
- Title: Subtitle
- Differential role for STIM1 in the regulation of vascular function (851.7)
- Creators
- Modar Kassan - 1EVMS Norfolk VA United StatesWei Zhang - University at Albany, State University of New YorkKarima Ait Aissa - EVMSJudith Stolwijk - University at Albany, State University of New YorkStefan Feske - New York UniversityMohamed Trebak - University at Albany, State University of New YorkKhalid Matrougui - 1EVMS Norfolk VA United States
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.28(S1), pp.851.7-n/a
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.28.1_supplement.851.7
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 04/2014
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984361722502771
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