Yue Yiyang, Meng Ke, Pu Yuejie, Zhang Xiaoming
College of Agriculture & Biotechnology, Zhejiang University, China.
School of Medicine, Zhejiang University, Hangzhou 310058, China.
Diabetes Res Clin Pract. 2017 Nov;133:124-130. doi: 10.1016/j.diabres.2017.08.018. Epub 2017 Sep 1.
Cardiovascular diseases account for the major cause of morbidity and mortality among individuals with diabetes. The diabetic cardiomyopathy (DCM) is a type of diabetic cardiovascular disease, which further directs to the heart failure. The researchers found that diabetes induced cardiac fibrosis plays a vital role in several of the pathological changes that associated with DCM, causing left ventricular hypertrophy (LVH), diastolic dysfunction and systolic dysfunction. However, the mechanisms involved in the pathogenesis of DCM are still elusive. Many studies have demonstrated that the transforming growth factor beta (TGF-β) is one of the molecular mediators implicated in the progression of fibrogenesis. In diabetes, hyperglycemia causes the expression changes of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), TGF-β genes, TGF-β proteins and their receptors. Activated TGF-β further leads to cardiac fibrosis, which in turn inducing DCM through the SMAD-dependent and independent pathways. Here, we reviewed the the molecular pathways that activate TGF-β then leading to cardiac fibrosis, which induced the pathological changes of DCM. Illustrating the pathways of TGF-ß would propose an efficient way for the management of diabetic cardiomyopathy (see Fig. 1).
心血管疾病是糖尿病患者发病和死亡的主要原因。糖尿病性心肌病(DCM)是糖尿病心血管疾病的一种类型,可进一步导致心力衰竭。研究人员发现,糖尿病诱导的心脏纤维化在与DCM相关的几种病理变化中起着至关重要的作用,可导致左心室肥厚(LVH)、舒张功能障碍和收缩功能障碍。然而,DCM发病机制所涉及的机制仍不明确。许多研究表明,转化生长因子β(TGF-β)是参与纤维化进展的分子介质之一。在糖尿病中,高血糖会导致微小RNA(miRNA)、长链非编码RNA(lncRNA)、TGF-β基因、TGF-β蛋白及其受体的表达变化。激活的TGF-β进一步导致心脏纤维化,进而通过SMAD依赖和非依赖途径诱导DCM。在此,我们综述了激活TGF-β进而导致心脏纤维化,从而引发DCM病理变化的分子途径。阐明TGF-β途径将为糖尿病性心肌病的治疗提供一种有效方法(见图1)。