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

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

  • Mol Cell Endocrinol. 2020 Dec 1;518:111005. doi: 10.1016/j.mce.2020.111005.
Shao-Hua Fan 1,  Qian-Feng Xiong 2,  Lei Wang 1,  Li-Hui Zhang 3,  Ya-Wei Shi 4
Affiliations

Affiliations

  • 1 Key Laboratory of Chemical Biology and Molecular Engineering, Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, 030006, Shanxi province, China.
  • 2 Key Laboratory of Chemical Biology and Molecular Engineering, Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, 030006, Shanxi province, China; Department of Cardiology, Fengcheng People's Hospital, Fengcheng, 331100, China.
  • 3 Department of Geriatrics, Shanxi Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, 030006, Shanxi province, China. Electronic address: [email protected].
  • 4 Key Laboratory of Chemical Biology and Molecular Engineering, Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan, 030006, Shanxi province, China. Electronic address: [email protected].
PMID: 32877753 DOI: 10.1016/j.mce.2020.111005
Abstract

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.

Keywords

ERK1/2; GLP-1; MMP1; NF-κB; Vascular remodelling.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13564
    98.92%, MMP Inhibitor
    MMP