1. 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
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José Luis Martín-Ventura, Jesús Egido, Emilio Camafeita, Jean-Baptiste Michel, Juan Antonio López, Luis Miguel Blanco-Colio, Julio Madrigal-Matute, Roxana Martinez-Pinna, Olivier Meilhac, César Aparicio, Melina Vega de Ceniga, Priscila Ramos-Mozo, Unión Europea. Comisión Europea, Ministerio de Ciencia e Innovación (España), Fundación Ramón Areces, Ministerio de Sanidad y Consumo (España), Instituto de Salud Carlos III, and Fundación ProCNIC
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Male ,Proteomics ,Neutrophils ,macromolecular substances ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Pathogenesis ,Andrology ,03 medical and health sciences ,chemistry.chemical_compound ,Aortic aneurysm ,0302 clinical medicine ,medicine ,Humans ,Electrophoresis, Gel, Two-Dimensional ,cardiovascular diseases ,Thrombus ,030304 developmental biology ,Aged ,Peroxidase ,Aged, 80 and over ,0303 health sciences ,biology ,Hydrogen Peroxide ,Middle Aged ,medicine.disease ,Catalase ,Abdominal aortic aneurysm ,Oxidative Stress ,chemistry ,Myeloperoxidase ,Case-Control Studies ,Immunology ,biology.protein ,Phorbol ,cardiovascular system ,Disease Progression ,Female ,Cardiology and Cardiovascular Medicine ,Oxidation-Reduction ,Oxidative stress ,Biomarkers ,Aortic Aneurysm, Abdominal - Abstract
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 H 2 O 2 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 H 2 O 2 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.