期刊
ATHEROSCLEROSIS
卷 221, 期 2, 页码 544-550出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2012.01.009
关键词
Biomarkers; Platelets; Thrombosis; Abdominal aortic aneurysm
资金
- Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Redes RECAVA [RD06/0014/0035, RD06/0014/0027, EUS2008-03565]
- Spanish MICIN [SAF 2010-21852]
- Basque Government [2008111019]
- EC, FAD [HEALTH F2-2008-200647]
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 > 50 mm) 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-3alpha (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 = 30-50 mm, 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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