Excessive Methionine Supplementation Exacerbates the Development of Abdominal Aortic Aneurysm in Rats

J Vasc Res. 2019;56(5):230-240. doi: 10.1159/000501313. Epub 2019 Jul 15.

Abstract

Objective: The relationship between methionine (Met) and abdominal aortic aneurysm (AAA) has been previously demonstrated, but the mechanisms controlling this association remain unclear. This study investigated the potential contribution of hypermethioninemia (HMet) to the development of AAA.

Methods: A model of AAA was induced by intraluminal porcine pancreatic elastase (PPE) infusion in 60 male Sprague-Dawley rats divided into 4 groups (n = 15 per group). Met was supplied by intragastric administration (1 g/kg body weight/day) from 1 week before surgery until 4 weeks after surgery. The aortic diameter was measured by ultrasound. Aortas were collected 4 weeks after surgery and subjected to biochemical analysis, histological assays, and transmission electron microscopy.

Results: After 5 weeks of Met supplementation, HMet increased the dilation ratio of the HMet + PPE group, and hyperhomocysteinemia was also induced in HMet and HMet + PPE rats. Increased matrix metalloproteinase-2 (MMP-2), osteopontin, and interleukin-6 expression was detected in HMet + PPE rats. Furthermore, increased autophagy was detected in the HMet + PPE group.

Conclusion: This study demonstrates that HMet may exacerbate the formation of AAA due to the increased dilation ratio partially via enhancing MMP-2 and inflammatory responses.

Keywords: Abdominal aortic aneurysm; Autophagy; Homocysteine; Matrix metalloproteinase-2; Methionine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / blood
  • Amino Acid Metabolism, Inborn Errors / chemically induced*
  • Animals
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / ultrastructure
  • Aortic Aneurysm, Abdominal / chemically induced*
  • Aortic Aneurysm, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / pathology
  • Dilatation, Pathologic
  • Disease Models, Animal
  • Disease Progression
  • Glycine N-Methyltransferase / blood
  • Glycine N-Methyltransferase / deficiency*
  • Interleukin-6 / metabolism
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Methionine*
  • Osteopontin / metabolism
  • Pancreatic Elastase
  • Rats, Sprague-Dawley
  • Risk Factors
  • Time Factors

Substances

  • Il6 protein, rat
  • Interleukin-6
  • Spp1 protein, rat
  • Osteopontin
  • Methionine
  • Glycine N-Methyltransferase
  • Pancreatic Elastase
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat

Supplementary concepts

  • Hypermethioninemia