Glucagon-like peptide-1 (GLP-1) and its split products GLP-1(9-37) and GLP-1(28-37) stabilize atherosclerotic lesions in apoe⁻/⁻ mice

Atherosclerosis. 2013 Dec;231(2):427-35. doi: 10.1016/j.atherosclerosis.2013.08.033. Epub 2013 Sep 5.


Background: [corrected] Glucagon-like peptide-1 (GLP-1) based therapies are new treatment options for patients with type 2 diabetes. Recent reports suggest vasoprotective actions of GLP-1. Similar beneficial effects might be reached by GLP-1(9-37) and the c-terminal GLP-1 split product (28-37) although both peptides do not activate the GLP-1 receptor. We therefore investigated the actions of GLP-1(7-37), GLP-1(9-37) as well as GLP-1(28-37) on vascular lesion formation in a mouse model of atherosclerosis.

Methods and results: GLP-1(7-37), GLP-1(9-37) and GLP-1(28-37) and LacZ (control) were overexpressed for a period of 12 weeks in apoe(-/-) mice on high-fat diet (n = 10/group) using an adeno-associated viral vector system. Neither of the constructs changed overall lesion size. However, GLP-1(7-37), GLP-1(9-37) and GLP-1(28-37) significantly reduced plaque macrophage infiltration (GLP-1(7-37): 40.6%, GLP-1(9-37): 47.0%, GLP-1(28-37): 40.1% decrease, p < 0.05) and plaque MMP-9 expression (GLP-1(7-37): 41.6%, GLP-1(9-37): 50.2%, GLP-1(28-37): 44.0% decrease, p < 0.05) compared to LacZ in the aortic arch. Moreover, all GLP-1 constructs increased plaque collagen content (GLP-1(7-37): 49.3%, GLP-1(9-37): 86.0%, GLP-1(28-37): 81.9% increase, p < 0.05) and increased fibrous cap thickness (GLP-1(7-37): 188.0%, GLP-1(9-37): 179.9% GLP-1(28-37): 111.0% increase, p < 0.05). These effects of GLP-1(7-37), GLP-1(9-37) and GLP-1(28-37) on plaque macrophage infiltration, MMP-9 expression and plaque collagen content were confirmed in the aortic root.

Conclusion: GLP-1(7-37), GLP-1(9-37) and GLP-1(28-37) reduce plaque inflammation and increase phenotypic characteristics of plaque stability in a murine model of atherosclerosis. Future studies are needed to determine whether these effects translate into improved plaque stability and less cardiovascular events in high-risk patients with type 2 diabetes.

Keywords: Atherosclerosis; GLP-1; Incretins; Plaque stability; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / blood*
  • Blood Glucose / metabolism
  • Collagen / metabolism
  • Diet, High-Fat
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Glucagon-Like Peptide 1 / metabolism*
  • Incretins / metabolism
  • Inflammation
  • Lipids / blood
  • Macrophages / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peptide Fragments / metabolism*
  • Phenotype
  • Plaque, Atherosclerotic / genetics
  • Transgenes


  • Apolipoproteins E
  • Blood Glucose
  • Incretins
  • Lipids
  • Peptide Fragments
  • Glucagon-Like Peptide 1
  • Collagen
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse