{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:10:01Z","timestamp":1792599001916,"version":"4.5.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,8,8]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The transient receptor potential vanilloid type 1 (\n              <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>\n              1) is expressed in the cardiovascular system, and increased\n              <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>\n              1 expression has been associated with cardiac hypertrophy. Nevertheless, the role of\n              <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>\n              1 in the pathogenesis of cardiac hypertrophy and the underlying molecular mechanisms remain unclear.\n            <\/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\">\n              In cultured cardiomyocytes, activation of\n              <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>\n              1 increased cell size and elevated expression of atrial natriuretic peptide\n              <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n              and intracellular calcium level, which was reversed by\n              <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>\n              1 antagonist capsazepine. Increased expression of phosphorylated calmodulin\u2010dependent protein kinase II\n              <jats:sub>\u03b4<\/jats:sub>\n              and mitogen\u2010activated protein kinases were found in\n              <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>\n              1 agonist capsaicin\u2010treated cardiomyocytes. Selective inhibitor of calmodulin\u2010dependent protein kinase II\n              <jats:sub>\u03b4<\/jats:sub>\n              decreased phosphorylation of extracellular signal\u2013regulated kinases and p38. Capsaicin induced an increase in expression of ornithine decarboxylase protein, which is the key enzyme in polyamine biosynthesis in cardiomyocytes. Nevertheless, there was no obvious change of ornithine decarboxylase expression in\n              <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>\n              1 knockdown cells after capsaicin treatment, and specific inhibitors of calmodulin\u2010dependent protein kinase II\n              <jats:sub>\u03b4<\/jats:sub>\n              or p38 downregulated the capsaicin\u2010induced expression of ornithine decarboxylase. Capsazepine alleviated the increase in cross\u2010sectional area of cardiomyocytes and the ratio of heart weight to body weight and improved cardiac function, including left ventricular internal end\u2010diastolic and \u2010systolic dimensions and ejection fraction and fractional shortening percentages, in mice treated with transverse aorta constriction. Capsazepine also reduced expression of ornithine decarboxylase and cardiac polyamine levels. Transverse aorta constriction induced increases in phosphorylated calmodulin\u2010dependent protein kinase II\n              <jats:sub>\u03b4<\/jats:sub>\n              and extracellular signal\u2013regulated kinases, and p38 and Serca2a were attenuated by capsazepine treatment.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              This study revealed that the mitogen\u2010activated protein kinase signaling pathway and intracellular polyamines are essential for\n              <jats:styled-content style=\"fixed-case\">TRPV<\/jats:styled-content>\n              1 activation\u2013induced cardiac hypertrophy.\n            <\/jats:p>\n          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