{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:57:12Z","timestamp":1789390632663,"version":"build-2803163510"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,12,6]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Metabolic syndrome is characterized by insulin resistance, which impairs intracellular signaling pathways and endothelial NO bioactivity, leading to cardiovascular complications. Extracellular signal\u2010regulated kinase (ERK) is a major component of insulin signaling cascades that can be activated by many vasoactive peptides, hormones, and cytokines that are elevated in metabolic syndrome. The aim of this study was to clarify the role of endothelial ERK2 in vivo on NO bioactivity and insulin resistance in a mouse model of metabolic syndrome.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Control and endothelial\u2010specific ERK2 knockout mice were fed a high\u2010fat\/high\u2010sucrose diet (HFHSD) for 24\u2009weeks. Systolic blood pressure, endothelial function, and glucose metabolism were investigated. Systolic blood pressure was lowered with increased NO products and decreased thromboxane A2\/prostanoid (TP) products in HFHSD\u2010fed ERK2 knockout mice, and N\u03c9\u2010nitro\u2010l\u2010arginine methyl ester (L\u2010NAME) increased it to the levels observed in HFHSD\u2010fed controls. Acetylcholine\u2010induced relaxation of aortic rings was increased, and aortic superoxide level was lowered in HFHSD\u2010fed ERK2 knockout mice. S18886, an antagonist of the TP receptor, improved endothelial function and decreased superoxide level only in the rings from HFHSD\u2010fed controls. Glucose intolerance and the impaired insulin sensitivity were blunted in HFHSD\u2010fed ERK2 knockout mice without changes in body weight. In vivo, S18886 improved endothelial dysfunction, systolic blood pressure, fasting serum glucose and insulin levels, and suppressed nonalcoholic fatty liver disease scores only in HFHSD\u2010fed controls.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Endothelial ERK2 increased superoxide level and decreased NO bioactivity, resulting in the deterioration of endothelial function, insulin resistance, and steatohepatitis, which were improved by a TP receptor antagonist, in a mouse model of metabolic syndrome.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027538","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T13:32:36Z","timestamp":1668605556000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Endothelial Extracellular Signal\u2010Regulated 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