{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:58:02Z","timestamp":1779926282299,"version":"3.53.1"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,7,7]]},"abstract":"<jats:sec xml:lang=\"en\"><jats:title>Background<\/jats:title><jats:p xml:lang=\"en\">Pro\u2010NTs (precursor of neurotrophins) and their receptor p75 are potential targets for preventing microvascular dysfunction induced by myocardial ischemia\u2013reperfusion injury (<jats:styled-content style=\"fixed-case\">IRI<\/jats:styled-content>). p75ECD (ectodomain of neurotrophin receptor p75) may physiologically produce neurocytoprotective effects by scavenging pro\u2010<jats:styled-content style=\"fixed-case\">NT<\/jats:styled-content>s. We therefore hypothesized that p75<jats:styled-content style=\"fixed-case\">ECD<\/jats:styled-content>may have a cardioprotective effect on<jats:styled-content style=\"fixed-case\">IRI<\/jats:styled-content>through microvascular mechanisms.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Methods and Results<\/jats:title><jats:p xml:lang=\"en\">Myocardial<jats:styled-content style=\"fixed-case\">IRI<\/jats:styled-content>was induced in Sprague\u2010Dawley rats by occluding the left main coronary arteries for 45\u00a0minutes before a subsequent relaxation. Compared with the ischemia\u2013reperfusion group, an intravenous injection of p75<jats:styled-content style=\"fixed-case\">ECD<\/jats:styled-content>(3\u00a0mg\/kg) 5\u00a0minutes before reperfusion reduced the myocardial infarct area at 24\u00a0hours after reperfusion (by triphenyltetrazolium chloride, 44.9\u00b13.9% versus 34.6\u00b15.7%,<jats:italic>P<\/jats:italic>&lt;0.05); improved the left ventricular ejection fraction (by echocardiography), with less myocardial fibrosis (by Masson's staining), and prevented microvascular dysfunction (by immunofluorescence) at 28\u00a0days after reperfusion; and reduced myocardial pro\u2010<jats:styled-content style=\"fixed-case\">NT<\/jats:styled-content>s expression at 24\u00a0hours and 28\u00a0days after reperfusion (by Western blotting). A simulative<jats:styled-content style=\"fixed-case\">IRI<\/jats:styled-content>model using rat microvascular pericytes was established in vitro by hypoxia\u2013reoxygenation (2\/6\u00a0hours) combined with pro\u2010<jats:styled-content style=\"fixed-case\">NT<\/jats:styled-content>s treatment (3\u00a0nmol\/L) at R. p75<jats:styled-content style=\"fixed-case\">ECD<\/jats:styled-content>(3\u00a0\u03bcg\/mL) given at R improved pericyte survival (by methyl thiazolyl tetrazolium assay) and attenuated apoptosis (by terminal deoxynucleotidyl transferase\u2010mediated dUTP\u2010biotin nick\u2010end labeling). In the reperfused hearts and hypoxia\u2013reoxygenation +pro\u2010<jats:styled-content style=\"fixed-case\">NT<\/jats:styled-content>s\u2010injured pericytes, p75<jats:styled-content style=\"fixed-case\">ECD<\/jats:styled-content>inhibited the expression of p\u2010JNK (phospho of c\u2010Jun N\u2010terminal kinase)\/caspase\u20103 (by Western blotting).<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>600125, an inhibitor of<jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>, did not enhance the p75<jats:styled-content style=\"fixed-case\">ECD<\/jats:styled-content>\u2010induced infarct\u2010sparing effects and pericyte protection.<\/jats:p><\/jats:sec><jats:sec xml:lang=\"en\"><jats:title>Conclusions<\/jats:title><jats:p xml:lang=\"en\">p75<jats:styled-content style=\"fixed-case\">ECD<\/jats:styled-content>may attenuate myocardial<jats:styled-content style=\"fixed-case\">IRI<\/jats:styled-content>via pro\u2010<jats:styled-content style=\"fixed-case\">NT<\/jats:styled-content>s reduction\u2010induced inhibition of p\u2010<jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>\/caspase\u20103 pathway of microvascular pericytes in rats.<\/jats:p><\/jats:sec>","DOI":"10.1161\/jaha.119.016047","type":"journal-article","created":{"date-parts":[[2020,6,20]],"date-time":"2020-06-20T10:20:22Z","timestamp":1592648422000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Recombinant Extracellular Domain (p75ECD) of the Neurotrophin Receptor p75 Attenuates Myocardial Ischemia\u2013Reperfusion Injury by Inhibiting the p\u2010JNK\/Caspase\u20103 Signaling Pathway in Rat Microvascular Pericytes"],"prefix":"10.1161","volume":"9","author":[{"given":"Jun","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Cardiology Fujian Heart Medical Center Fujian Institute of Coronary Heart Disease Fujian Medical University Union Hospital Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiXiong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Cardiology Fujian Heart Medical Center Fujian Institute of Coronary Heart Disease Fujian Medical University Union Hospital Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DeDong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology Fujian Heart Medical Center Fujian Institute of Coronary Heart Disease Fujian Medical University Union Hospital Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Cardiology Fujian Heart Medical Center Fujian Institute of Coronary Heart Disease Fujian Medical University Union Hospital Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HuaShan","family":"Hong","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Vascular Aging Department of Geriatrics Fujian Institute of Geriatrics Fujian Medical University Union Hospital Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DanQing","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Fujian Heart Medical Center Fujian Institute of Coronary Heart Disease Fujian Medical University Union Hospital Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YunLing","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cardiology Fujian Heart Medical Center Fujian Institute of Coronary Heart Disease Fujian Medical University Union Hospital Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoLiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science Chinese Academy of Medical Sciences &amp; Comparative Medicine Centre, Peking Union Medical Collage, and Beijing Collaborative Innovation Center for Cardiovascular Disorders Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LingZhen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Fujian Heart Medical Center Fujian Institute of Coronary Heart Disease Fujian Medical University Union Hospital Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TingXiang","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Cardiology Fujian Heart Medical Center Fujian Institute of Coronary Heart Disease Fujian Medical University Union Hospital Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiWei","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science Chinese Academy of Medical Sciences &amp; Comparative Medicine Centre, Peking Union Medical Collage, and Beijing Collaborative Innovation Center for Cardiovascular Disorders Beijing P. R. 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