Plasma profiling by a protein array approach identifies IGFBP-1 as a novel biomarker of abdominal aortic aneurysm

Objective: Cytokines are important mediators of immune-inflammatory responses implicated in abdominal aortic aneurysm (AAA) pathogenesis. Our objective was to investigate the cytokine expression profile in plasma of AAA patients. Methods: Cytokine protein expression was measured in plasma of 5 large...

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Detalles Bibliográficos
Autores: Ramos-Mozo, P., Rodriguez, C., Pastor Vargas, Carlos, Blanco-Colio, L.M., Martinez-Gonzalez, J., Meilhac, O., Michel, J-B, Vega de Ceniga, M., Egido, J., Martin-Ventura, J.L.
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/107275
Acceso en línea:https://hdl.handle.net/20.500.14352/107275
Access Level:acceso abierto
Palabra clave:611.1
616.12-005
Biomarkers
Platelets
Thrombosis
Abdominal aortic aneurysm
Sistema cardiovascular
3207.04 Patología Cardiovascular
Descripción
Sumario:Objective: Cytokines are important mediators of immune-inflammatory responses implicated in abdominal aortic aneurysm (AAA) pathogenesis. Our objective was to investigate the cytokine expression profile in plasma of AAA patients. Methods: Cytokine protein expression was measured in plasma of 5 large AAA patients (aortic size >50mm) and 5 controls (aortic size <30 mm) using a 20-cytokine antibody-based protein array. IGFBP-1 plasma concentrations were analyzed by ELISA. IGFBP-1 protein levels were analyzed in AAA thrombus by immunohistochemistry and Western blot. Platelet aggregation was assessed by conventional optical aggregometry. Results: Several proteins including MIP-3 alpha (CCL20), Eotaxin-2 and IGFBP-1 were increased in AAA patients compared to controls. Among them, IGFBP-1 concentrations were significantly higher in large AAA patients vs control subjects. These data were validated in plasma of patients with large AAA (n = 30) compared to matched controls (n = 30) [834(469-1628) vs 497(204-893) pg/ml, p<0.01]. Furthermore, the potential association of IGFBP-1 with AAA size was analyzed in a second independent group of subjects [large AAA (n = 59), small AAA patients (aortic size = 30-50mm, n = 54) and controls (n = 30)]. Interestingly, IGFBP-1 levels correlated with AAA size (r = 0.4, p<0.001), which remained significant after adjusting for traditional risk factors. IGFBP-1 was localized in the luminal part of AAA thrombus and IGFBP-1 levels were increased in AAA thrombus conditioned media compared to media layer and healthy media. Interestingly, IGFBP-1 abrogated the potentiation of ADP-induced platelet aggregation triggered by IGF-1. Conclusions: IGFBP-1 has been identified by a protein array approach as a potential novel biomarker of AAA. The biological role of IGFBP-1 in AAA pathogenesis could be related to the modulation on the effect of IGF-1 on platelet aggregation.