背景:糖尿病(DM)是世界上最常见的心血管疾病危险因素之一,到2021年患病率超过5亿人口。心脏纤维化及其复杂过程被认为是解释糖尿病患者心力衰竭发展的机制之一。最近,高血糖背景下心脏纤维化的生物分子机制一直集中在转化生长因子β-1(TGFβ-1)作为主要因子。然而,包括microRNAs(miRNAs)在内的多种因子具有相互作用的作用,microRNAs是与TGFβ-1相关的心肌纤维化的潜在调节因子。在这次审查中,我们探讨了多种因素的相互作用作用,包括在糖尿病中与TGFβ-1相关的作为心肌纤维化潜在调节因子的microRNA.这篇叙述性综述包括过去10年(2012-2022年)出版的PubMed和ScienceDirect数据库的文章。
方法:在糖尿病患者中,肌成纤维细胞的过度激活发生,并触发前胶原蛋白转化为成熟的胶原蛋白以填充心脏间质空间,导致细胞外基质重塑的病理过程。基质金属蛋白酶(MMP)与其抑制剂(金属蛋白酶的组织抑制剂,TIMP)在细胞外基质的降解中至关重要。糖尿病相关的心脏纤维化是通过增加细胞成分介导的TGF-β1水平来调节的,包括心肌细胞和涉及成纤维细胞的非心肌细胞,血管周细胞平滑肌细胞,内皮细胞,肥大细胞,巨噬细胞,和树突状细胞。一些miRNA,如miR-21,miR-9,miR-29,miR-30d,miR-144,miR-34a,miR-150、miR-320和miR-378在糖尿病心肌病中上调。TGF-β1与炎性细胞因子一起,氧化应激,SMA和母亲联合对抗截瘫(SMAD)蛋白质,丝裂原活化蛋白激酶(MAPK),和microRNAs,与细胞外基质的产生和纤维化反应相关。在这次审查中,我们探讨了多种因素的相互作用作用,包括在糖尿病中与TGFβ-1相关的作为心肌纤维化潜在调节因子的microRNA.
结论:长期高血糖通过涉及TGF-β1、miRNA、炎性趋化因子,氧化应激,SMAD,或MAPK途径。最近有越来越多的证据表明miRNA在调节心脏纤维化中的作用。
BACKGROUND: Diabetes mellitus (DM) is among the most common risk factors for cardiovascular disease in the world with prevalence of more than 500 million population in 2021. Cardiac fibrosis with its complex process has been hypothesized as one of the mechanisms explaining development of heart failure in diabetic patients. Recently, the biomolecular mechanism of cardiac fibrosis in the hyperglycemia setting has been focusing around transforming growth factor β-1 (TGFβ-1) as a major factor. However, there is interplay role of several factors including microRNAs (miRNAs) which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1. In this
review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus. This narrative
review included articles from the PubMed and Science Direct databases published in the last 10 years (2012-2022).
METHODS: In diabetic patients, excessive activation of myofibroblasts occurs and triggers pro-collagen to convert into mature collagen to fill the cardiac interstitial space resulting in a pathological process of extracellular matrix remodeling. The balance between matrix metalloproteinase (MMP) and its inhibitor (tissue inhibitor of metalloproteinase, TIMP) is crucial in degradation of the extracellular matrix. Diabetes-related cardiac fibrosis is modulated by increasing level of TGF-β1 mediated by cellular components, including cardiomyocyte and non-cardiomyocyte cells involving fibroblasts, vascular pericytes smooth muscle cells, endothelial cells, mast cells, macrophages, and dendritic cells. Several miRNAs such as miR-21, miR-9, miR-29, miR-30d, miR-144, miR-34a, miR-150, miR-320, and miR-378 are upregulated in diabetic cardiomyopathy. TGF-β1, together with inflammatory cytokines, oxidative stress, combined sma and the mothers against decapentaplegic (smad) protein, mitogen-activated protein kinase (MAPK), and microRNAs, is interconnectedly involved in extracellular matrix production and fibrotic response. In this
review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus.
CONCLUSIONS: Long-term hyperglycemia activates cardiac fibroblast via complex processes involving TGF-β1, miRNA, inflammatory chemokines, oxidative stress, smad, or MAPK pathways. There is increasing evidence of miRNA\'s roles lately in modulating cardiac fibrosis.