{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T07:52:34Z","timestamp":1793433154111,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2018,12,7]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Physical exercise provides benefits for various organ systems, and some of systemic effects of exercise are mediated through modulation of muscle-derived secreted factors, also known as myokines. Myonectin\/C1q (complement component 1q)\/TNF (tumor necrosis factor)-related protein 15\/erythroferrone is a myokine that is upregulated in skeletal muscle and blood by exercise.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>We investigated the role of myonectin in myocardial ischemic injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Ischemia-reperfusion in myonectin-knockout mice led to enhancement of myocardial infarct size, cardiac dysfunction, apoptosis, and proinflammatory gene expression compared with wild-type mice. Conversely, transgenic overexpression of myonectin in skeletal muscle reduced myocardial damage after ischemia-reperfusion. Treadmill exercise increased circulating myonectin levels in wild-type mice, and it reduced infarct size after ischemia-reperfusion in wild-type mice, but not in myonectin-knockout mice. Treatment of cultured cardiomyocytes with myonectin protein attenuated hypoxia\/reoxygenation-induced apoptosis via S1P (sphingosine-1-phosphate)-dependent activation of cAMP\/Akt cascades. Similarly, myonectin suppressed inflammatory response to lipopolysaccharide in cultured macrophages through the S1P\/cAMP\/Akt-dependent signaling pathway. Moreover, blockade of S1P-dependent pathway reversed myonectin-mediated reduction of myocardial infarct size in mice after ischemia-reperfusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>These data indicate that myonectin functions as an endurance exercise-induced myokine which ameliorates acute myocardial ischemic injury by suppressing apoptosis and inflammation in the heart, suggesting that myonectin mediates some of the beneficial actions of exercise on cardiovascular health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.118.313777","type":"journal-article","created":{"date-parts":[[2018,12,6]],"date-time":"2018-12-06T14:01:02Z","timestamp":1544104862000},"page":"1326-1338","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":175,"title":["Myonectin Is an Exercise-Induced Myokine That Protects the Heart From Ischemia-Reperfusion Injury"],"prefix":"10.1161","volume":"123","author":[{"given":"Naoya","family":"Otaka","sequence":"first","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. Murohara), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Advanced Cardiovascular Therapeutics (R.S.), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Cardiology (K.O., T.E., N. Ouchi), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Uemura","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. Murohara), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kambara","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. Murohara), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Cardiology (K.O., T.E., N. Ouchi), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Ogawa","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. Murohara), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Ito","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. Murohara), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kawanishi","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. Murohara), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonomi","family":"Maruyama","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. Murohara), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Joki","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. Murohara), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Fujikawa","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. Murohara), Nagoya University Graduate School of Medicine, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Narita","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (N. Otaka, Y.U., T.K., H.O., M.I., H.K., S.M., Y.J., Y.F., S.N., K.U., T. 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