{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:23:54Z","timestamp":1783488234971,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY20H020005"],"award-info":[{"award-number":["LY20H020005"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Previous studies have shown that trimetazidine (TMZ) alleviates diabetes\u2010induced cardiac dysfunction. However, the underlying mechanism for its protective effects on cardiac function remains incompletely understood. Diminished autophagy was found in diabetic hearts, and restoration of autophagy generates cardioprotective effect. This study aims to investigate whether and how TMZ produces protective effect through increasing autophagic activity in the diabetic heart.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A high\u2010fat diet and low\u2010dose streptozotocin were applied to induce type 2 diabetes mellitus (T2DM) in male C57BL\/6 mice, followed by treatment with TMZ for 14\u2009weeks before cardiac function was evaluated. To mimic the diabetic condition, the neonatal rat cardiomyocytes (NRCMs) were exposed to high glucose\/palmitic acid (HP) in the presence or absence of TMZ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that TMZ treatment promotes autophagic flux in cardiomyocytes, which is impaired in diabetes. We further found that the AMPK and lncRNA H19 played critical roles in mediating TMZ\u2010induced enhancement of autophagy in cardiomyocyte. We showed that TMZ treatment restored the level of H19 and phosphorylated AMPK (p\u2010AMPK T172) in diabetic heart and NRCMs exposed to HP. Of note, the effect of TMZ on autophagy and p\u2010AMPK was abolished by knockdown of H19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings indicated that TMZ is able to recover the cardiac autophagic activity which is impaired by T2DM, and the underlying mechanism accounted for this ability is mostly likely attributed to the restored expression of H19 and AMPK activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1440-1681.70006","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:49:46Z","timestamp":1731977386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Trimetazidine restores autophagy via <scp>lncRNA H19<\/scp>\/<scp>AMPK<\/scp> in diabetic heart: Implications for its therapeutic value against diabetic cardiomyopathy"],"prefix":"10.1111","volume":"52","author":[{"given":"Wei","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Cardiology Zhejiang Hospital  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Health Zhejiang Hospital  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danjun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Health Zhejiang Hospital  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Health Zhejiang Hospital  Hangzhou 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