Angiotensin-Converting Enzyme 2 Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysms in Mice

Hum Gene Ther. 2018 Dec;29(12):1387-1395. doi: 10.1089/hum.2016.144. Epub 2018 Nov 13.

Abstract

Recent studies have demonstrated that angiotensin-converting enzyme 2 (ACE2) plays an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). However, few studies have reported the direct effect of ACE2 overexpression on the aneurysm. This study hypothesized that the overexpression of ACE2 may prevent the pathogenesis of aneurysms by decreasing RAS activation. Thirty-nine mice were randomly assigned to three groups (n = 13 in each group): the Ad.ACE2 group, the Ad.EGFP group, and a control group. After 8 weeks of treatment, abdominal aortas with AAAs were obtained for hematoxylin and eosin staining, Verhoeff Van Gieson staining, immunohistochemistry, and Western blotting. The incidence and severity of AAAs, macrophage infiltration, and MMP protein expression were all recorded. The results showed that ACE2 gene transfer significantly decreased the occurrence of AAAs and inhibited AAA formation in ApoE-/- mice by inhibiting the inflammatory response and MMP activation, and the mechanisms may involve decreased ERK and Ang II-nuclear factor kappa B signaling pathways.

Keywords: ACE2; MMP; aneurysm; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Angiotensin II / administration & dosage*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Aorta, Abdominal / drug effects
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / chemically induced
  • Aortic Aneurysm, Abdominal / genetics
  • Aortic Aneurysm, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / prevention & control*
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Blotting, Western
  • Disease Models, Animal
  • Gene Expression Regulation
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 1 / genetics*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / metabolism
  • Signal Transduction

Substances

  • Apolipoproteins E
  • NF-kappa B
  • enhanced green fluorescent protein
  • Angiotensin II
  • Green Fluorescent Proteins
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • Matrix Metalloproteinase 13
  • Mmp13 protein, mouse