A plethora of studies have demonstrated that cardiomyopathy represents a serious source of morbidity and mortality in patients with diabetes. Yet, the underlying mechanisms of diabetic cardiomyopathy are still poorly understood. Of interest, cytochrome P450 2J (CYP2J) and soluble epoxide hydrolase (sEH) are known to control the maintenance of cardiovascular health through the regulation of cardioprotective epoxyeicosatrienoic acids (EETs) and its less active products, dihydroxyeicosatrienoic acids (DHETs). Therefore, we examined the role of the aforementioned pathway in the development of diabetic cardiomyopathy. Our diabetic model initiated cardiomyopathy as indexed by the increase in the expression of hypertrophic markers such as NPPA. Furthermore, diabetic cardiomyopathy was associated with a low level of cardiac EETs and an increase of the DHETs/EETs ratio both in vivo and in cardiac cells. The modulation in EETs and DHETs was attributed to the increase of sEH and the decrease of CYP2J. Interestingly, the reduction of sEH attenuates cardiotoxicity mediated by high glucose in cardiac cells. Mechanistically, the beneficial effect of sEH reduction might be due to the decrease of phosphorylated ERK1/2 and p38. Overall, the present work provides evidence that diabetes initiates cardiomyopathy through the increase in sEH, the reduction of CYP2J, and the decrease of cardioprotective EETs.
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http://dx.doi.org/10.1097/FJC.0000000000000707 | DOI Listing |
World J Cardiol
January 2025
Department of Cardiology, Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan 030012, Shanxi Province, China.
This article discusses the study by Grubić Rotkvić on the mechanisms of action of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF). T2DM and HF are highly comorbid, with a significantly increased prevalence of HF in patients with T2DM. SGLT2i exhibit potential in reducing hospitalization rates for HF and cardiovascular mortality through multiple mechanisms, including improving blood glucose control, promoting urinary sodium excretion, reducing sympathetic nervous system activity, lowering both preload and afterload on the heart, alleviating inflammation and oxidative stress, enhancing endothelial function, improving myocardial energy metabolism, and stabilizing cardiac ion homeostasis.
View Article and Find Full Text PDFClin Epigenetics
January 2025
Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
Diabetic cardiomyopathy (DbCM), a significant chronic complication of diabetes, manifests as myocardial hypertrophy, fibrosis, and other pathological alterations that substantially impact cardiac function and elevate the risk of cardiovascular diseases and patient mortality. Myocardial energy metabolism disturbances in DbCM, encompassing glucose, fatty acid, ketone body and lactate metabolism, are crucial factors that contribute to the progression of DbCM. In recent years, novel protein post-translational modifications (PTMs) such as lactylation, β-hydroxybutyrylation, and succinylation have been demonstrated to be intimately associated with the myocardial energy metabolism process, and in conjunction with acetylation, they participate in the regulation of protein activity and gene expression activity in cardiomyocytes.
View Article and Find Full Text PDFMetabolism
January 2025
Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Chang-Le Xi Street #127, Xi' an 710032, China. Electronic address:
The nonenergy-producing or biomass-accumulating functions of metabolism are attracting increasing attention, as metabolic changes are gaining importance as discrete signaling pathways in modulating enzyme activity and gene expression. Substantial evidence suggests that myocardial metabolic remodeling occurring during diabetic cardiomyopathy, heart failure, and cardiac pathological stress (e.g.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Department of Biomedical Sciences, Grand Valley State University, Allendale, MI 49401, USA.
Background: Diabetes mellitus is associated with morphological and functional impairment of the heart primarily due to lipid toxicity caused by increased fatty acid metabolism. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) have been implicated in the metabolism of fatty acids in the liver and skeletal muscles. However, their role in the heart in diabetes remains unclear.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Medical School, University of Cyprus, 1678 Nicosia, Cyprus.
Diabetes mellitus (DM) is a multifaceted disorder with a pandemic spread and a remarkable burden of cardiovascular mortality and morbidity. Diabetic cardiomyopathy (DBCM) has been increasingly recognized as the development of cardiac dysfunction, which is accompanied by heart failure (HF) symptoms in the absence of obvious reasons like ischemic heart disease, hypertension, or valvulopathies. Several pathophysiological mechanisms have been proposed, including metabolic disorders (e.
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