{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:35:48Z","timestamp":1784864148425,"version":"3.55.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>MAPKs (mitogen-activated protein kinases), especially p38, play detrimental roles in cardiac diseases and cardiac remodeling post-myocardial infarction. However, the activation and function of MAPKs in coronary thrombosis in vivo and its relationship with clinical outcomes remain poorly understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>Here, we showed that p38\u03b1 was the major isoform expressed in human and mouse platelets. Platelet-specific p38\u03b1-deficient mice presented impaired thrombosis and hemostasis but had improved cardiac function, reduced infarct size, decreased inflammatory response, and microthrombus in a left anterior descending artery ligation model. Signaling analysis revealed that p38 activation was one of the earliest events in platelets after treatment with receptor agonists or reactive oxygen species. p38\u03b1\/MAPK-activated protein kinase 2\/heat shock protein 27 and p38\u03b1\/cytosolic phospholipases A2 were the major pathways regulating receptor-mediated or hydrogen peroxide-induced platelet activation in an ischemic environment. Moreover, the distinct roles of ERK1\/2 (extracellular signal\u2013regulated kinase) in receptor- or reactive oxygen species-induced p38-mediated platelet activation reflected the complicated synergistic relationships among MAPKs. Analysis of clinical samples revealed that MAPKs were highly phosphorylated in platelets from preoperative patients with ST-segment\u2013elevation myocardial infarction, and increased phosphorylation of p38 was associated with no-reflow outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>We conclude that p38\u03b1 serves as a critical regulator of platelet activation and potential indicator of highly thrombotic lesions and no-reflow, and inhibition of platelet p38\u03b1 may improve clinical outcomes in subjects with ST-segment\u2013elevation myocardial infarction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.309856","type":"journal-article","created":{"date-parts":[[2017,10,6]],"date-time":"2017-10-06T00:10:28Z","timestamp":1507248628000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Platelet-Specific p38\u03b1 Deficiency Improved Cardiac Function After Myocardial Infarction in Mice"],"prefix":"10.1161","volume":"37","author":[{"given":"Panlai","family":"Shi","sequence":"first","affiliation":[{"name":"From the Department of Biochemistry and Molecular Cell Biology (P.S., L.Z., K.W., X.F., J.L.), Department of Cardiology, Ninth People\u2019s Hospital (M.Z., W.Y., J.Z.), and Shanghai Institute of Immunology (G.H.), Shanghai Jiao Tong University School of Medicine, China; 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and Cardiovascular Division, King\u2019s College London British Heart Foundation Centre of Research Excellence, United Kingdom (K.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Yang","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Molecular Cell Biology (P.S., L.Z., K.W., X.F., J.L.), Department of Cardiology, Ninth People\u2019s Hospital (M.Z., W.Y., J.Z.), and Shanghai Institute of Immunology (G.H.), Shanghai Jiao Tong University School of Medicine, China; and Cardiovascular Division, King\u2019s College London British Heart Foundation Centre of Research Excellence, United Kingdom (K.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kemin","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Molecular Cell Biology (P.S., L.Z., K.W., X.F., J.L.), Department of Cardiology, Ninth People\u2019s Hospital (M.Z., W.Y., J.Z.), and Shanghai Institute of Immunology (G.H.), Shanghai Jiao Tong University School of Medicine, China; 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