Comparative proteomics reveals a systemic vulnerability in the vasculature of patients with abdominal aortic aneurysms

J Vasc Surg. 2011 Oct;54(4):1100-1108.e6. doi: 10.1016/j.jvs.2011.04.038. Epub 2011 Jul 13.

Abstract

Introduction: Abdominal aortic aneurysms (AAA) are associated with inflammation, apoptosis, and matrix degradation. AAA tissue represents the end stage of disease, limiting its utility in identification of factors culpable for initiation of aneurysm development. Recent evidence suggests that AAAs are a local representation of a systemic disease of the vasculature. Morphologic and molecular changes, comparable to those found in the aneurysm wall, have been demonstrated in veins from patients with AAAs. Changes in the vascular tissue proteome of patients with AAAs were investigated, using inferior mesenteric vein (IMV), to gain insight into early molecular changes contributing to AAA development.

Methods: IMV was harvested from 16 patients with AAA and 16 matched controls. Whole IMV lysates were subjected to 2-D difference in gel electrophoresis (2D-DIGE) with quantitative densitometry. Protein spots differentially expressed in AAA were identified using mass spectrometry. Differential protein expression was validated by Western blotting and localized to cell type by immunohistochemistry (IHC).

Results: Decreased levels of prohibitin (AAA, 2.00 ± 1.37; controls, 3.81 ± 1.39; 1.9-fold change; P = .02) AAA (7.33 ± 3.9; controls, 14.5 ± 5.6; 2-fold change; P = .001), along with relative increases in a cleaved fragment of vimentin (AAA, 12.9 ± 9; controls, 6.9 ± 4.7; 2-fold change; P = .11) were identified in AAA patients. All proteins were localized to the vascular smooth muscle cells.

Conclusions: Proteins important in combating the injurious effects of oxidative stress and modulating the response to inflammation appear reduced in the vasculature of patients with AAA. These changes may represent early events in AAA formation. Enhancing expression of these proteins might offer a novel therapeutic avenue to inhibit AAA development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Annexin A1 / analysis
  • Aorta, Abdominal / chemistry
  • Aortic Aneurysm, Abdominal / metabolism*
  • Blotting, Western
  • Case-Control Studies
  • Densitometry
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Humans
  • Immunohistochemistry
  • London
  • Male
  • Mass Spectrometry
  • Mesenteric Veins / chemistry
  • Middle Aged
  • Muscle, Smooth, Vascular / chemistry*
  • Myocytes, Smooth Muscle / chemistry*
  • Proteins / analysis*
  • Proteomics* / methods
  • Repressor Proteins / analysis
  • Reproducibility of Results
  • Vimentin / analysis

Substances

  • Annexin A1
  • Proteins
  • Repressor Proteins
  • Vimentin
  • prohibitin