Cardiovascular protective effects of GLP-1: a focus on the MAPK signaling pathway

Biochem Cell Biol. 2022 Feb;100(1):9-16. doi: 10.1139/bcb-2021-0365. Epub 2021 Oct 16.

Abstract

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.

Keywords: cardiovascular disease; diabète de type 2; glucagon-like peptide 1; maladies cardiovasculaires; mitogen-activated protein kinase pathway; peptide GLP-1; type 2 diabetes; voie de la MAPK.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptide-1 Receptor / therapeutic use
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Signal Transduction

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptide 1
  • Mitogen-Activated Protein Kinases