Plasma profiling by a protein array approach identifies IGFBP-1 as a novel biomarker of abdominal aortic aneurysm.
2012, Atherosclerosis. 2012 Jan 25. [Epub ahead of print]
Ramos-Mozo P, Rodriguez C, Pastor-Vargas C, Blanco-Colio LM, Martinez-Gonzalez J, Meilhac O, Michel JB, de Ceniga MV, Egido J, Martin-Ventura JL
Autors del centre relacionats: Martínez-González Jose, Rodríguez Cristina.
Ramos-Mozo P, Rodriguez C, Pastor-Vargas C, Blanco-Colio LM, Martinez-Gonzalez J, Meilhac O, Michel JB, de Ceniga MV, Egido J, Martin-Ventura JL
Autors del centre relacionats: Martínez-González Jose, Rodríguez Cristina.
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 <30mm) 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=30-50mm, 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.
METHODS: Cytokine protein expression was measured in plasma of 5 large AAA patients (aortic size >50mm) and 5 controls (aortic size <30mm) 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=30-50mm, 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.
Institut Català de Ciències Cardiovasculars
Hospital de la Santa Creu i Sant Pau, Pavelló del Convent
Sant Antoni Maria Claret, 167 08025 Barcelona
Espanya
T: +34 - 93 556 5900 F: +34 - 93 556 5559