{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:16:25Z","timestamp":1791000985560,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic cardiomyopathy (DCM) is a cardiac disorder, which affects around 12% diabetic patients, resulting in overt heart death. Our initial bioinformatic analysis identified the differentially expressed gene 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010coenzyme A synthase 2 (HMGCS2) in DCM, which may be activated by peroxisome proliferator\u2010activated receptor\u2010alpha (PPAR\u03b1) based on previous evidence. Therefore, the present study aims to explore the effect of PPAR\u03b1 on the development of DCM through regulating HMGCS2. The expression of PPAR\u03b1 and HMGCS2 was detected by reverse transcription quantitative polymerase chain reaction in cardiomyocytes and high\u2010glucose\u2010cultured cardiomyocytes. The proliferation and apoptosis of cardiomyocytes were examined by 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine assay and flow cytometry, separately. Mitoehondrial membrane potential (MMP) and intracellular reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) levels were determined. Then, the protein levels of B\u2010cell lymphoma 2, Bcl\u20102\u2010associated X protein, and cleaved Caspase\u20103 were detected by Western blot analysis. The myocardial apoptosis index, heart weight, and serum lipids of rats were examined. At last, the expressions of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transforming growth factor \u03b21 (TGF\u03b21), peroxisome proliferator activator receptor gamma coactivator\u20101 alpha (PGC1\u03b1), nuclear respiratory factor (NRF)\u20101, NRF\u20102, NAD(P)H oxidase 1, and superoxide dismutase\u20101 were examined. HMGCS2 was the most differentially expressed gene in DCM. The levels of HMGCS2 and PPAR\u03b1 were upregulated in patients with DCM. HMGCS2 silencing was shown to inhibit HMGCS2 expression to suppress the apoptosis of high\u2010glucose\u2010induced cardiomyocytes and the loss of MMP, reduce the accumulation of ROS, and promote cardiomyocyte proliferation. Silencing of HMGCS2 and PPAR\u03b1 alleviated myocardial injury, decreased blood glucose, and lipid in DCM rats, downregulated the expression of ANP, BNP, and TGF\u03b21 to reduce myocardial injury, and elevated PGC1\u03b1, NRF\u20101, and NRF\u20102 levels to enhance oxidative stress levels. Our results demonstrated that silencing of PPAR\u03b1 could alleviate cardiomyocyte injury and oxidative stress via a mechanism related to the downregulation of HMGCS2, which could provide a novel target for DCM treatment.<\/jats:p>","DOI":"10.1002\/iub.2337","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T04:28:22Z","timestamp":1596169702000},"page":"1997-2009","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Silencing of peroxisome proliferator\u2010activated receptor\u2010alpha alleviates myocardial injury in diabetic cardiomyopathy by downregulating 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010coenzyme A synthase 2 expression"],"prefix":"10.1002","volume":"72","author":[{"given":"Li","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrine Rizhao Traditional Chinese Medicine Hospital  Rizhao 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