{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:27:53Z","timestamp":1790645273623,"version":"4.1.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec>\n            <jats:title>Objectives\u2014<\/jats:title>\n            <jats:p>Chronic hypertension is the most critical risk factor for cardiovascular disease, heart failure, and stroke.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Here we show that wild-type mice infused with angiotensin II develop hypertension, cardiac hypertrophy, perivascular fibrosis, and endothelial dysfunction with enhanced stromal interaction molecule 1 (STIM1) expression in heart and vessels. All these pathologies were significantly blunted in mice lacking STIM1 specifically in smooth muscle (Stim1\n              <jats:sup>SMC\u2212\/\u2212<\/jats:sup>\n              ). Mechanistically, STIM1 upregulation during angiotensin II\u2013induced hypertension was associated with enhanced endoplasmic reticulum stress, and smooth muscle STIM1 was required for endoplasmic reticulum stress\u2013induced vascular dysfunction through transforming growth factor-\u03b2 and nicotinamide adenine dinucleotide phosphate oxidase\u2013dependent pathways. Accordingly, knockout mice for the endoplasmic reticulum stress proapoptotic transcriptional factor, CCAAT-enhancer\u2013binding protein homologous protein (CHOP\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ), were resistant to hypertension-induced cardiovascular pathologies. Wild-type mice infused with angiotensin II, but not Stim1\n              <jats:sup>SMC\u2212\/\u2212<\/jats:sup>\n              or CHOP\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice showed elevated vascular nicotinamide adenine dinucleotide phosphate oxidase activity and reduced phosphorylated endothelial nitric oxide synthase, cGMP, and nitrite levels.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Thus, smooth muscle STIM1 plays a crucial role in the development of hypertension and associated cardiovascular pathologies and represents a promising target for cardiovascular therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.116.307869","type":"journal-article","created":{"date-parts":[[2016,7,29]],"date-time":"2016-07-29T03:33:00Z","timestamp":1469763180000},"page":"1900-1909","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":65,"title":["Essential Role of Smooth Muscle STIM1 in Hypertension and Cardiovascular Dysfunction"],"prefix":"10.1161","volume":"36","author":[{"given":"Modar","family":"Kassan","sequence":"first","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karima","family":"Ait-Aissa","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Radwan","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Mali","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Haddox","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohanad","family":"Gabani","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souad","family":"Belmadani","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaikobad","family":"Irani","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Trebak","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); Department of Physiological Sciences, EVMS, Norfolk, VA (M.K., K.A.-A., E.R., V.M., S.H., S.B., K.M.); Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, PA (W.Z., M.T); and Department of Internal Medicine, University of Iowa, Iowa City (K.M., M.G., K.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Matrougui","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University, New Orleans, LA (M.K., K.M.); 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