title: Differential role for stromal interacting molecule 1 in the regulation of vascular function.
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.
authors: Department of Physiological Sciences, EVMS, Norfolk, VA, 23501, USA.
authors: Modar
authors: M
authors: Kassan
authors: Wei
authors: W
authors: Zhang
authors: Karima Ait
authors: KA
authors: Aissa
authors: Judith
authors: J
authors: Stolwijk
authors: Mohamed
authors: M
authors: Trebak
authors: Khalid
authors: K
authors: Matrougui
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009928:Organ Specificity; D010656:Phenylephrine / Q000494:pharmacology; D000071737:Stromal Interaction Molecule 1; D013931:Thromboxanes / Q000494:pharmacology; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
chemical_list: D015220:Calcium Channels; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D010656:Phenylephrine