Wang Gang, Lin Fang, Wan Qin, Wu Jianbo, Luo Mao
Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China; Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, the School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
Department of Endocrinology, Nephropathy Clinical Medical Research Center of Sichuan Province, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Pharmacol Res. 2021 Feb;164:105390. doi: 10.1016/j.phrs.2020.105390. Epub 2020 Dec 19.
Angiogenesis is rapidly initiated in response to pathological conditions and is a key target for pharmaceutical intervention in various malignancies. Anti-angiogenic therapy has emerged as a potential and effective therapeutic strategy for treating cancer and cardiovascular-related diseases. Metformin, a first-line oral antidiabetic agent for type 2 diabetes mellitus (T2DM), not only reduces blood glucose levels and improves insulin sensitivity and exerts cardioprotective effects but also shows benefits against cancers, cardiovascular diseases, and other diverse diseases and regulates angiogenesis. MicroRNAs (miRNAs) are endogenous noncoding RNA molecules with a length of approximately 19-25 bases that are widely involved in controlling various human biological processes. A large number of miRNAs are involved in the regulation of cardiovascular cell function and angiogenesis, of which miR-21 not only regulates vascular cell proliferation, migration and apoptosis but also plays an important role in angiogenesis. The relationship between metformin and abnormal miRNA expression has gradually been revealed in the context of numerous diseases and has received increasing attention. This paper reviews the drug-target interactions and drug repositioning events of metformin that influences vascular cells and has benefits on angiogenesis-mediated effects. Furthermore, we use miR-21 as an example to explain the specific molecular mechanism underlying metformin-mediated regulation of the miRNA signaling pathway controlling angiogenesis and vascular protective effects. These findings may provide a new therapeutic target and theoretical basis for the clinical prevention and treatment of cardiovascular diseases.
血管生成在病理条件下迅速启动，是各种恶性肿瘤药物干预的关键靶点。抗血管生成治疗已成为治疗癌症和心血管相关疾病的一种潜在且有效的治疗策略。二甲双胍是2型糖尿病（T2DM）的一线口服抗糖尿病药物，不仅能降低血糖水平、改善胰岛素敏感性并发挥心脏保护作用，还对癌症、心血管疾病和其他多种疾病有益，并能调节血管生成。微小RNA（miRNA）是长度约为19 - 25个碱基的内源性非编码RNA分子，广泛参与调控各种人类生物学过程。大量miRNA参与心血管细胞功能和血管生成的调节，其中miR - 21不仅调节血管细胞的增殖、迁移和凋亡，还在血管生成中起重要作用。在众多疾病背景下，二甲双胍与异常miRNA表达之间的关系逐渐被揭示，并受到越来越多的关注。本文综述了二甲双胍影响血管细胞并对血管生成介导效应有益的药物 - 靶点相互作用和药物重新定位事件。此外，我们以miR - 21为例，解释二甲双胍介导调控控制血管生成和血管保护作用的miRNA信号通路的具体分子机制。这些发现可能为心血管疾病的临床预防和治疗提供新的治疗靶点和理论基础。
