Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
Sunshine Coast Health Institute, University of the Sunshine Coast, Birtinya, QLD 4575, Australia.
Int J Biol Sci. 2021 May 11;17(8):2050-2068. doi: 10.7150/ijbs.59965. eCollection 2021.
Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.
2 型糖尿病(T2DM)与心血管疾病(CVD)密切相关,包括动脉粥样硬化、高血压和心力衰竭。一些抗糖尿病药物与体重增加或低血糖风险增加有关,这可能会降低这些治疗方法预期的抗高血糖效果。最近开发的胰高血糖素样肽-1(GLP-1RAs)受体激动剂,可刺激胰岛素分泌并降低糖化血红蛋白水平,而不会产生体重增加和低血糖等副作用。此外,GLP1-RAs 在有或没有糖尿病的受试者中表现出多种心血管保护作用。已经有几项涉及 GLP-1RAs 的心血管结局试验(CVOTs),这些试验支持了这些药物的整体心血管益处。GLP-1RAs 降低血浆脂质水平和血压(BP),这两者都有助于减少动脉粥样硬化和降低 CVD。GLP-1R 在多种心血管细胞类型中表达,如单核细胞/巨噬细胞、平滑肌细胞、内皮细胞和心肌细胞。最近的研究表明,对内皮功能障碍的保护特性、对巨噬细胞的抗炎作用以及对平滑肌细胞的抗增殖作用,可能通过 GLP-1R 信号传导有助于动脉粥样保护。在本综述中,我们描述了 GLP-1RAs 在 CVOTs、动物模型和培养细胞中的心血管作用及其潜在的作用机制,并探讨了这些发现如何改变我们对 T2DM 药物治疗和 CVD 预防的理解。
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