Department of Internal Medicine, Division of Cardiovascular Medicine, University of Nevada Las Vegas School of Medicine, Las Vegas, NV, 89102, USA.
Department of Biomedical Engineering, Schools of Medicine and Engineering, University of Alabama at Birmingham, University Blvd., Birmingham, AL, 35294, USA.
Cardiovasc Diabetol. 2023 Feb 20;22(1):37. doi: 10.1186/s12933-023-01755-1.
Diabetes mellitus is one of the prime risk factors for cardiovascular complications and is linked with high morbidity and mortality. Diabetic cardiomyopathy (DCM) often manifests as reduced cardiac contractility, myocardial fibrosis, diastolic dysfunction, and chronic heart failure. Inflammation, changes in calcium (Ca) handling and cardiomyocyte loss are often implicated in the development and progression of DCM. Although the existence of DCM was established nearly four decades ago, the exact mechanisms underlying this disease pathophysiology is constantly evolving. Furthermore, the complex pathophysiology of DCM is linked with exosomes, which has recently shown to facilitate intercellular (cell-to-cell) communication through biomolecules such as micro RNA (miRNA), proteins, enzymes, cell surface receptors, growth factors, cytokines, and lipids. Inflammatory response and Ca signaling are interrelated and DCM has been known to adversely affect many of these signaling molecules either qualitatively and/or quantitatively. In this literature review, we have demonstrated that Ca regulators are tightly controlled at different molecular and cellular levels during various biological processes in the heart. Inflammatory mediators, miRNA and exosomes are shown to interact with these regulators, however how these mediators are linked to Ca handling during DCM pathogenesis remains elusive. Thus, further investigations are needed to understand the mechanisms to restore cardiac Ca homeostasis and function, and to serve as potential therapeutic targets in the treatment of DCM.
糖尿病是心血管并发症的主要危险因素之一，与高发病率和死亡率有关。糖尿病心肌病（DCM）常表现为心肌收缩力降低、心肌纤维化、舒张功能障碍和慢性心力衰竭。炎症、钙（Ca）处理变化和心肌细胞丢失常与 DCM 的发生和发展有关。尽管 DCM 的存在已经确立了近四十年，但这种疾病病理生理学的确切机制仍在不断发展。此外，DCM 的复杂病理生理学与外泌体有关，外泌体最近通过诸如 micro RNA (miRNA)、蛋白质、酶、细胞表面受体、生长因子、细胞因子和脂质等生物分子促进细胞间（细胞间）通讯。炎症反应和 Ca 信号相互关联，DCM 已知会对这些信号分子的许多进行定性和/或定量的不利影响。在这篇文献综述中，我们已经证明 Ca 调节剂在心脏的各种生物过程中在不同的分子和细胞水平上受到严格控制。炎症介质、miRNA 和外泌体被证明与这些调节剂相互作用，但是这些介质如何与 DCM 发病机制期间的 Ca 处理相关仍然难以捉摸。因此，需要进一步的研究来了解恢复心脏 Ca 稳态和功能的机制，并作为 DCM 治疗的潜在治疗靶点。
