De Akash, Sarkar Arnab, Banerjee Tanmoy, Bhowmik Rudranil, Sar Shuvam, Shaharyar Md Adil, Karmakar Sanmoy, Ghosh Nilanjan
Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
Molecular Pharmacology Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
Front Pharmacol. 2025 Jul 23;16:1613844. doi: 10.3389/fphar.2025.1613844. eCollection 2025.
Diabetic cardiomyopathy (DCM) is a prominent contributor to morbidity and mortality in people with diabetes worldwide. In diabetic patients, it is a chronic condition that is characterized by ventricular hypertrophy (VH), diastolic dysfunction, alteration of systolic function, and reduced ejection fraction, ultimately leading to heart failure (HF). Despite being extensively understood, the underlying causes of DCM remain obscure. Growing evidence has identified the contribution of microRNAs (miRNAs), a small non-coding RNA molecule playing a crucial part in the pathogenesis of DCM. These miRNAs have been linked with several mechanistic pathways involved in DCM, including inflammation, insulin resistance and cardiomyocyte apoptosis. miRNAs related to DCM include miR-9, 30d, 34a, 142-3p, 144, 150, 208a, etc. Thus, miRNAs present themselves as novel targets for diagnostic biomarkers and mechanistic therapeutics, which may prove to be clinically more efficient than other therapeutic approaches. This review highlights the role of miRNAs, which can act as the nodes of signalling networks that regulate the progression of DCM and also tries to decipher the complicated cross-talk between miRNAs and DCM-related signalling pathways through various protein factors modulation, which includes RyR-2, TGF-β, IGF-1R, NF-κB and Nrf-2 and also immunological regulation of cardiomyocytes. There has also been a discussion of diagnostic and therapeutic management of various miRNAs in the management of DCM with recent clinical trials on diabetes and cardiovascular disorder with miRNA candidates and concluded with the future perspective of miRNAs as new novel theranostic tools in the emerging field of diagnostic and therapeutic management.
糖尿病性心肌病(DCM)是全球糖尿病患者发病和死亡的主要原因。在糖尿病患者中,它是一种慢性疾病,其特征为心室肥厚(VH)、舒张功能障碍、收缩功能改变和射血分数降低,最终导致心力衰竭(HF)。尽管人们对此已有广泛了解,但DCM的潜在病因仍不明确。越来越多的证据表明,微小RNA(miRNA)在DCM的发病机制中起着关键作用,这种小的非编码RNA分子参与了DCM的发病过程。这些miRNA与DCM涉及的多种机制途径相关,包括炎症、胰岛素抵抗和心肌细胞凋亡。与DCM相关的miRNA包括miR-9、30d、34a、142-3p、144、150、208a等。因此,miRNA成为诊断生物标志物和机制性治疗的新靶点,可能比其他治疗方法在临床上更有效。本综述强调了miRNA的作用,其可作为调节DCM进展的信号网络节点,并试图通过各种蛋白质因子调节来解读miRNA与DCM相关信号通路之间复杂的相互作用,这些蛋白质因子包括兰尼碱受体2(RyR-2)、转化生长因子-β(TGF-β)、胰岛素样生长因子-1受体(IGF-1R)、核因子-κB(NF-κB)和核因子E2相关因子2(Nrf-2),以及心肌细胞的免疫调节。还讨论了各种miRNA在DCM管理中的诊断和治疗应用,以及最近关于糖尿病和心血管疾病的miRNA候选物的临床试验,并以miRNA作为诊断和治疗管理新兴领域中新的诊断治疗工具的未来前景作为总结。
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