Background: Diabetes is associated with myocardial fibrosis, while the underlying mechanisms remain elusive. The aim of this study is to investigate the underlying role of calcineurin/nuclear factor of activated T cell 3 (CaN/NFATc3) pathway and the Enhancer of zeste homolog 2 (EZH2) in diabetes-related myocardial fibrosis.
Methods: Streptozotocin (STZ)-injected diabetic rats were randomized to two groups: the controlled glucose (Con) group and the diabetes mellitus (DM) group. Eight weeks later, transthoracic echocardiography was used for cardiac function evaluation, and myocardial fibrosis was visualized by Masson trichrome staining. The primary neonatal rat cardiac fibroblasts were cultured with high-glucose medium with or without cyclosporine A or GSK126. The expression of proteins involved in the pathway was examined by western blotting. The nuclear translocation of target proteins was assessed by immunofluorescence.
Results: The results indicated that high glucose treatment increased the expression of CaN, NFATc3, EZH2 and trimethylates lysine 27 on histone 3 (H3K27me3) in vitro and in vivo. The inhibition of the CaN/NFATc3 pathway alleviated myocardial fibrosis. Notably, inhibition of CaN can inhibit the nuclear translocation of NFATc3, and the expression of EZH2 and H3K27me3 protein induced by high glucose. Moreover, treatment with GSK126 also ameliorated myocardial fibrosis.
Conclusion: Diabetes can possibly promote myocardial fibrosis by activating of CaN/NFATc3/EZH2 pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512648 | PMC |
| http://dx.doi.org/10.1186/s12872-023-03492-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effects of genetic mutations on left ventricular myocardial mechanics and fibrosis patterns in hypertrophic cardiomyopathy.
Sci Rep
January 2025
Division of Cardiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Myocyte disarray and fibrosis are underlying pathologies of hypertrophic cardiomyopathy (HCM) caused by genetic mutations. However, the extent of their contributions has not been extensively evaluated. In this study, we investigated the effects of genetic mutations on myofiber function and fibrosis patterns in HCM.
View Article and Find Full Text PDFMyocardial Disease in Systemic Sclerosis: Recent Updates and Clinical Implications.
Curr Cardiol Rep
January 2025
Johns Hopkins University Division of Cardiology, Baltimore, MD, USA.
Purpose Of Review: The present review aims to address systemic sclerosis (SSc)-associated myocardial disease, a significant cause of morbidity and mortality, by examining the mechanisms of inflammation, microvascular dysfunction, and fibrosis that drive cardiac involvement. The objective is to elucidate critical risk factors and explore advanced diagnostic tools for early detection, enhancing patient outcomes by identifying those at highest risk.
Recent Findings: Recent studies underscore the importance of specific autoantibody profiles, disease duration, and cardiovascular comorbidities as key risk factors for severe cardiac manifestations in SSc.
TRADD-mediated pyroptosis contributes to diabetic cardiomyopathy.
Acta Pharmacol Sin
January 2025
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
Regulated cell death like pyroptosis is one vital cause of diabetic cardiomyopathy (DCM), which eventually leads to heart failure. Tumor necrosis factor (TNF) receptor-associated death domain protein (TRADD) is an adapter protein with multiple functions that participates in the pathophysiological progress of different cardiovascular disorders via regulating regulated cell death. Studies have shown that TRADD combines with receptor-interacting protein kinase 3 (RIPK3) and facilitates its activation, thereby mediating TNF-induced necroptosis.
View Article and Find Full Text PDFDihydrotanshinone I improves cardiac function by promoting lymphangiogenesis after myocardial ischemia-reperfusion injury.
Eur J Pharmacol
January 2025
Academy of Integrated Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:
Dihydrotanshinone I (DHT) is an active ingredient derived from Salvia miltiorrhiza. Previous studies have demonstrated that DHT can improve cardiac function in rats with myocardial ischemia-reperfusion injury (IR). However, the mechanism by which DHT improves myocardial injury in rats still requires further research.
View Article and Find Full Text PDFCardiac pathology associated with hypertension and chronic kidney disease in aged cats.
J Comp Pathol
January 2025
Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK. Electronic address:
Hypertension is a common condition in older cats, often secondary to chronic kidney disease (CKD). Although the heart is one of the organs damaged by hypertension, the pathology of the feline hypertensive (HT) heart has been poorly studied. The aim of this retrospective study was to describe the gross and microscopic pathology of hearts obtained from cats at post-mortem examination and to compare cats diagnosed with hypertension with cats of similar age and kidney function for which antihypertensive treatment was not deemed clinically necessary.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!