| First Author | Shi P | Year | 2017 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 37 |
| Issue | 12 | Pages | e185-e196 |
| PubMed ID | 28982666 | Mgi Jnum | J:269191 |
| Mgi Id | MGI:6272092 | Doi | 10.1161/ATVBAHA.117.309856 |
| Citation | Shi P, et al. (2017) Platelet-Specific p38alpha Deficiency Improved Cardiac Function After Myocardial Infarction in Mice. Arterioscler Thromb Vasc Biol 37(12):e185-e196 |
| abstractText | OBJECTIVE: 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. APPROACH AND RESULTS: Here, we showed that p38alpha was the major isoform expressed in human and mouse platelets. Platelet-specific p38alpha-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. p38alpha/MAPK-activated protein kinase 2/heat shock protein 27 and p38alpha/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-regulated 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-elevation myocardial infarction, and increased phosphorylation of p38 was associated with no-reflow outcomes. CONCLUSIONS: We conclude that p38alpha serves as a critical regulator of platelet activation and potential indicator of highly thrombotic lesions and no-reflow, and inhibition of platelet p38alpha may improve clinical outcomes in subjects with ST-segment-elevation myocardial infarction. |
