{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:21:34Z","timestamp":1792448494158,"version":"4.5.0"},"reference-count":66,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:p>\n                    Reactive oxygen species (ROS) induce matrix metalloproteinase (MMP) activity that mediates hypertrophy and cardiac remodeling. Adiponectin (APN), an adipokine, modulates cardiac hypertrophy, but it is unknown if APN inhibits ROS-induced cardiomyocyte remodeling. We tested the hypothesis that APN ameliorates ROS-induced cardiomyocyte remodeling and investigated the mechanisms involved. Cultured adult rat ventricular myocytes (ARVM) were pretreated with recombinant APN (30 \u03bcg\/ml, 18 h) followed by exposure to physiologic concentrations of H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    (1\u2013200 \u03bcM). ARVM hypertrophy was measured by [\n                    <jats:sup>3<\/jats:sup>\n                    H]leucine incorporation and atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) gene expression by RT-PCR. MMP activity was assessed by in-gel zymography. ROS was induced with angiotensin (ANG)-II (3.2 mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7day\n                    <jats:sup>\u22121<\/jats:sup>\n                    for 14 days) in wild-type (WT) and APN-deficient (APN-KO) mice. Myocardial MMPs, tissue inhibitors of MMPs (TIMPs), p-AMPK, and p-ERK protein expression were determined. APN significantly decreased H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced cardiomyocyte hypertrophy by decreasing total protein, protein synthesis, ANF, and BNP expression. H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced MMP-9 and MMP-2 activities were also significantly diminished by APN. APN significantly increased p-AMPK in both nonstimulated and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -treated ARVM. H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced p-ERK activity and NF-\u03baB activity were both abrogated by APN pretreatment. ANG II significantly decreased myocardial p-AMPK and increased p-ERK expression in vivo in APN-KO vs. WT mice. ANG II infusion enhanced cardiac fibrosis and MMP-2-to-TIMP-2 and MMP-9-to-TIMP-1 ratios in APN-KO vs. WT mice. Thus APN inhibits ROS-induced cardiomyocyte remodeling by activating AMPK and inhibiting ERK signaling and NF-\u03baB activity. Its effects on ROS and ultimately on MMP expression define the protective role of APN against ROS-induced cardiac remodeling.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00428.2011","type":"journal-article","created":{"date-parts":[[2011,6,11]],"date-time":"2011-06-11T00:30:19Z","timestamp":1307752219000},"page":"H984-H993","source":"Crossref","is-referenced-by-count":95,"title":["Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling"],"prefix":"10.1152","volume":"301","author":[{"given":"Eric E.","family":"Essick","sequence":"first","affiliation":[{"name":"Whitaker Cardiovascular Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Ouchi","sequence":"additional","affiliation":[{"name":"Whitaker Cardiovascular Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Whitaker Cardiovascular 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