Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China.
Research Laboratory of Translational Medicine, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, People's Republic of China.
Biochem Cell Biol. 2022 Feb;100(1):9-16. doi: 10.1139/bcb-2021-0365. Epub 2021 Oct 16.
Cardiovascular and related metabolic diseases are significant global health challenges. Glucagon-like peptide 1 (GLP-1) is a brain-gut peptide secreted by the ileal endocrine system and is now an established drug target in type 2 diabetes (T2DM). GLP-1 targeting agents have been shown not only to treat T2DM, but also to exert cardiovascular protective effects by regulating multiple signaling pathways. The mitogen-activated protein kinase (MAPK) pathway, a common signal transduction pathway for transmitting extracellular signals to downstream effector molecules, is involved in regulating diverse cellular physiological processes, including cell proliferation, differentiation, stress, inflammation, functional synchronization, transformation, and apoptosis. The purpose of this review is to highlight the relationship between GLP-1 and cardiovascular disease (CVD) and discuss how GLP-1 exerts cardiovascular protective effects through the MAPK signaling pathway. This review also discusses the future challenges in fully characterizing and evaluating the CVD protective effects of GLP-1 receptor agonists (GLP-1RA) at the cellular and molecular levels. A better understanding of the MAPK signaling pathway that is dysregulated in CVD may aid in the design and development of promising GLP-1RA.
心血管及相关代谢疾病是全球性的重大健康挑战。胰高血糖素样肽 1(GLP-1)是一种由回肠内分泌系统分泌的脑肠肽,现已成为 2 型糖尿病(T2DM)的既定药物靶点。GLP-1 靶向药物不仅可用于治疗 T2DM,还可通过调节多种信号通路发挥心血管保护作用。丝裂原活化蛋白激酶(MAPK)通路是一种将细胞外信号传递至下游效应分子的常见信号转导通路,参与调节多种细胞生理过程,包括细胞增殖、分化、应激、炎症、功能同步、转化和凋亡。本综述旨在强调 GLP-1 与心血管疾病(CVD)之间的关系,并探讨 GLP-1 通过 MAPK 信号通路发挥心血管保护作用的机制。本综述还讨论了在细胞和分子水平上充分描述和评估 GLP-1 受体激动剂(GLP-1RA)对 CVD 保护作用的未来挑战。更好地了解 CVD 中失调的 MAPK 信号通路可能有助于设计和开发有前途的 GLP-1RA。