4.7 Article

Proteomic Analysis of Polymorphonuclear Neutrophils Identifies Catalase as a Novel Biomarker of Abdominal Aortic Aneurysm: Potential Implication of Oxidative Stress in Abdominal Aortic Aneurysm Progression

Journal

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 31, Issue 12, Pages 3011-U619

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.111.237537

Keywords

aneurysms; antioxidants; leukocytes

Funding

  1. European Commission [HEALTH F2-2008-200647]
  2. Spanish Ministerio de Ciencia e Innovacion [SAF2010/21852]
  3. Fundacion Ramon Areces
  4. Ministerio de Sanidad y Consumo
  5. Instituto de Salud Carlos III
  6. Redes RECAVA [(RD06/0014/0035), EUS2008-03565]
  7. Fundacion Pro CNIC

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Objective-Polymorphonuclear neutrophils (PMNs) play a main role in abdominal aortic aneurysm (AAA) progression. We have analyzed circulating PMNs isolated from AAA patients and controls by a proteomic approach to identify proteins potentially involved in AAA pathogenesis. Methods and Results-PMNs from 8 AAA patients (4 large AAA >5 cm and 4 small AAA 3-5 cm) and 4 controls were analyzed by 2D differential in-gel electrophoresis. Among differentially expressed spots, several proteins involved in redox balance were identified by mass spectrometry (eg, cyclophilin, thioredoxin reductase, catalase). Diminished catalase expression and activity were observed in PMNs from AAA patients compared with controls. In contrast, PMNs from AAA patients displayed higher H2O2 and myeloperoxidase levels than PMNs from controls. Moreover, a significant decrease in catalase mRNA levels was observed in PMNs after phorbol 12-myristate 13-acetate incubation. Catalase plasma levels were also decreased in large (n=47) and small (n=56) AAA patients compared with controls (n=34). We observed catalase expression in AAA thrombus and thrombus-conditioned medium, associated with PMN infiltration. Furthermore, increased H2O2 levels were observed in AAA thrombus-conditioned medium compared with the media layer. Conclusion-Diminished catalase levels in circulating PMNs and plasma are observed in AAA patients, supporting an important role of oxidative stress in AAA evolution. (Arterioscler Thromb Vasc Biol. 2011;31:3011-3019.)

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