Glucagon-like peptide 1 treatment reverses vascular remodelling by downregulating matrix metalloproteinase 1 expression through inhibition of the ERK1/2/NF-κB signalling pathway

• Published in: Molecular and cellular endocrinology Vol. 518; p. 111005
• Main Authors: Fan, Shao-Hua, Xiong, Qian-Feng, Wang, Lei, Zhang, Li-Hui, Shi, Ya-Wei
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2020
• Subjects: agonists; collagen; diastolic blood pressure; ERK1/2; extracellular matrix; GLP-1; glucagon-like peptide 1; hypertension; interstitial collagenase; MMP1; NF-κB; noninsulin-dependent diabetes mellitus; rats; smooth muscle; systolic blood pressure; therapeutics; Vascular remodelling; SBP; T2DM; GLP-1; WKY; MMP1; RAS; AT1R; HR; BP; ECM; DPP4; NF-κB; FAK; ERK1/2; Vascular remodelling; DBP; PI3K; RASMC; VSMC; SHR; AngII; p38MAPK; GLP-1R
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2020.111005

In addition to serving as an incretin-based treatment of type 2 diabetes mellitus (T2DM), glucagon-like peptide 1 (GLP-1) can also reverse cardiovascular diseases caused by vascular remodelling. However, a detailed mechanism underlying how GLP-1 reverses vascular remodelling remains unclear. Here, Spontaneous hypertension rats (SHR) were used as an in vivo model of vascular remodelling. Treatment with a GLP-1 receptor (GLP-1R) agonist Liraglutide or dipeptidyl peptidase 4 (DPP4) inhibitor Alogliptin decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), thickness of vascular wall, and overall collagen levels in SHR. In vitro vascular remodelling can be induced by exposing rat aortic smooth muscle cells (RASMC) to angiotensin II (Ang II); GLP-1 treatment attenuated AngII induction of RASMC proliferation, migration, and excessive extracellular matrix (ECM) degradation. Downregulation of matrix metalloproteinase 1 (MMP1) enhanced the inhibitory effects of GLP-1, and extracellular regulated protein kinase 1/2 (ERK1/2) and nuclear factor kappa-B (NF-κB) signalling participated in these processes. These results provide a new mechanistic understanding of key therapeutic strategies for the treatment of vascular remodelling-related diseases. •GLP-1 reverse vascular remodelling.•The role of MMP1 in vascular remodelling was described for the first time.•ERK1/2-NF-κB signalling pathway plays an important role in GLP-1 reverse vascular remodelling.•MMP1 could used be as a therapeutic target for diseases caused by vascular remodelling.