{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:15:43Z","timestamp":1790712943754,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,6,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Heart failure, caused by sustained pressure overload, remains a major public health problem. PKM (pyruvate kinase M) acts as a rate\u2010limiting enzyme of glycolysis. PKM2 (pyruvate kinase M2), an alternative splicing product of PKM, plays complex roles in various biological processes and diseases. However, the role of PKM2 in the development of heart failure remains unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Cardiomyocyte\u2010specific\n              <jats:italic>Pkm2<\/jats:italic>\n              knockout mice were generated by crossing the floxed\n              <jats:italic>Pkm2<\/jats:italic>\n              mice with \u03b1\u2010MHC (myosin heavy chain)\u2010Cre transgenic mice, and cardiac specific\n              <jats:italic>Pkm2<\/jats:italic>\n              overexpression mice were established by injecting adeno\u2010associated virus serotype 9 system. The results showed that cardiomyocyte\u2010specific\n              <jats:italic>Pkm2<\/jats:italic>\n              deletion resulted in significant deterioration of cardiac functions under pressure overload, whereas\n              <jats:italic>Pkm2<\/jats:italic>\n              overexpression mitigated transverse aortic constriction\u2010induced cardiac hypertrophy and improved heart functions. Mechanistically, we demonstrated that PKM2 acted as a protein kinase rather than a pyruvate kinase, which inhibited the activation of RAC1 (rho family, small GTP binding protein)\u2010MAPK (mitogen\u2010activated protein kinase) signaling pathway by phosphorylating RAC1 in the progress of heart failure. In addition, blockade of RAC1 through NSC23766, a specific RAC1 inhibitor, attenuated pathological cardiac remodeling in\n              <jats:italic>Pkm2<\/jats:italic>\n              deficiency mice subjected to transverse aortic constriction.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">This study revealed that PKM2 attenuated overload\u2010induced pathological cardiac hypertrophy and heart failure, which provides an attractive target for the prevention and treatment of cardiomyopathies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.024854","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T10:40:00Z","timestamp":1654252800000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Pyruvate Kinase M2 Protects Heart from Pressure 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