Research Article| Volume 221, ISSUE 2, P544-550, April 2012

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



      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.


      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.


      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.


      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.


      • IGFBP-1 has been identified by a protein array as a novel biomarker of AAA.
      • IGFBP-1 concentration are increased in AAA.
      • IGFBP-1 levels correlated with AAA size.
      • IGFBP-1 was localized in the luminal part of AAA thrombus.
      • IGFBP-1 abrogated the effect of IGF-1 in ADP-induced platelet aggregation.


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        • Sakalihasan N.
        • Limet R.
        • Defawe O.D.
        Abdominal aortic aneurysm.
        Lancet. 2005; 365: 1577-1589
        • Michel J.B.
        • Martin-Ventura J.L.
        • Egido J.
        • et al.
        Novel aspects of the pathogenesis of aneurysms of the abdominal aorta in humans.
        Cardiovasc Res. 2011; 90: 18-27
        • Baxter B.T.
        • Terrin M.C.
        • Dalman R.L.
        Medical management of small abdominal aortic aneurysms.
        Circulation. 2008; 117: 1883-1889
        • Urbonavicius S.
        • Urbonaviciene G.
        • Honore B.
        • Henneberg E.W.
        • Vorum H.
        • Lindholt J.S.
        Potential circulating biomarkers for abdominal aortic aneurysm expansion and rupture—a systematic review.
        Eur J Vasc Endovasc Surg. 2008; 36: 273-280
        • Golledge J.
        • Tsao P.S.
        • Dalman R.L.
        • Norman P.E.
        Circulating markers of abdominal aortic aneurysm presence and progression.
        Circulation. 2008; 118: 2382-2392
        • Blanco-Colio L.M.
        • Lopez J.A.
        • Martinez-Pinna R.
        • Egido J.
        • Martin-Ventura J.L.
        Vascular proteomics, a translational approach: from traditional to novel proteomic techniques.
        Expert Rev Proteomics. 2009; 6: 461-464
        • Nordon I.
        • Brar R.
        • Hinchliffe R.
        • Cockerill G.
        • Loftus I.
        • Thompson M.
        The role of proteomic research in vascular disease.
        J Vasc Surg. 2009; 49: 1602-1612
        • Granger J.
        • Siddiqui J.
        • Copeland S.
        • Remick D.
        Albumin depletion of human plasma also removes low abundance proteins including the cytokines.
        Proteomics. 2005; 5: 4713-4718
        • Schwenk J.M.
        • Igel U.
        • Kato B.S.
        • et al.
        Comparative protein profiling of serum and plasma using an antibody suspension bead array approach.
        Proteomics. 2010; 10: 532-540
        • Martinez-Pinna R.
        • Barbas C.
        • Blanco-Colio L.M.
        • et al.
        Proteomic and metabolomic profiles in atherothrombotic vascular disease.
        Curr Atheroscler Rep. 2010; 12: 202-208
        • Golledge A.L.
        • Walker P.
        • Norman P.E.
        • Golledge J.
        A systematic review of studies examining inflammation associated cytokines in human abdominal aortic aneurysm samples.
        Dis Markers. 2009; 26: 181-188
        • Golledge J.
        • Clancy P.
        • Moran C.
        • et al.
        The novel association of the chemokine CCL22 with abdominal aortic aneurysm.
        Am J Pathol. 2010; 176: 2098-2106
        • Caligiuri G.
        • Rossignol P.
        • Julia P.
        • et al.
        Reduced immunoregulatory CD31+ T cells in patients with atherosclerotic abdominal aortic aneurysm.
        Arterioscler Thromb Vasc Biol. 2006; 26: 618-623
        • Badimon L.
        • Martínez-González J.
        • Royo T.
        • Lassila R.
        • Badimon J.J.
        A sudden increase in plasma epinephrine levels transiently enhances platelet deposition on severely damaged arterial wall.
        Thromb Haemost. 1999; 82: 1736-1742
        • Motani A.S.
        • Anggård E.E.
        • Ferns G.A.
        Recombinant insulin-like growth factor-1 modulates aggregation in human platelets via extracellular calcium.
        Life Sci. 1996; 58: PL269-PL274
        • Kodali R.
        • Hajjou M.
        • Berman A.B.
        • et al.
        Chemokines induce matrix metalloproteinase-2 through activation of epidermal growth factor receptor in arterial smooth muscle cells.
        Cardiovasc Res. 2006; 69: 706-715
        • van Kuijk J.P.
        • Flu W.J.
        • Chonchol M.
        • Bax J.J.
        • Verhagen H.J.
        • Poldermans D.
        Metabolic syndrome is an independent predictor of cardiovascular events in high-risk patients with occlusive and aneurysmatic peripheral arterial disease.
        Atherosclerosis. 2010; 210: 596-601
        • Lang C.H.
        • Nystrom G.J.
        • Frost R.A.
        Tissue-specific regulation of IGF-I and IGF-binding proteins in response to TNFalpha.
        Growth Horm IGF Res. 2001; 11: 250-260
        • Norman P.
        • Le M.
        • Pearce C.
        • Jamrozik K.
        Infrarenal aortic diameter predicts all-cause mortality.
        Arterioscler Thromb Vasc Biol. 2004; 24: 1278-1282
        • Houard X.
        • Rouzet F.
        • Touat Z.
        • et al.
        Topology of the fibrinolytic system within the mural thrombus of human abdominal aortic aneurysms.
        J Pathol. 2007; 212: 20-28
        • Houard X.
        • Touat Z.
        • Ollivier V.
        • et al.
        Mediators of neutrophil recruitment in human abdominal aortic aneurysms.
        Cardiovasc Res. 2009; 82: 532-541
        • Panek B.
        • Gacko M.
        • Pałka J.
        Metalloproteinases, insulin-like growth factor-I and its binding proteins in aortic aneurysm.
        Int J Exp Pathol. 2004; 85: 159-164
        • Gibson T.L.
        • Cohen P.
        Inflammation-related neutrophil proteases, cathepsin G and elastase, function as insulin-like growth factor binding protein proteases.
        Growth Horm IGF Res. 1999; 9: 241-253
        • Mañes S.
        • Mira E.
        • Barbacid M.M.
        • et al.
        Identification of insulin-like growth factor-binding protein-1 as a potential physiological substrate for human stromelysin-3.
        J Biol Chem. 1997; 272: 25706-25712
        • Wheatcroft S.B.
        • Kearney M.T.
        IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis.
        Trends Endocrinol Metab. 2009; 20: 153-162
        • Motani A.
        • Rutherford C.
        • Anggard E.E.
        • Ferns G.A.
        Insulin-like growth factor binding protein-1 inhibits arterial smooth muscle cell proliferation in vitro but does not reduce the neointimal response to balloon catheter injury.
        Atherosclerosis. 1995; 118: 57-66
        • Gustafsson T.
        • Andersson P.
        • Arnqvist H.J.
        Different inhibitory actions of IGFBP-1, -2 and -4 on IGF-I effects in vascular smooth muscle cells.
        J Endocrinol. 1999; 161: 245-253
        • Karey K.P.
        • Sirbasku D.A.
        Human platelet-derived mitogens, II: subcellular localization of insulin like growth factor I to the alpha-granule and release in response to thrombin.
        Blood. 1989; 74: 1093-1100
        • Myronovych A.
        • Murata S.
        • Chiba M.
        • et al.
        Role of platelets on liver regeneration after 90% hepatectomy in mice.
        J Hepatol. 2008; 49: 363-372
        • Marcinkiewicz M.
        • Gordon P.V.
        A role for plasmin in platelet aggregation: differential regulation of IGF release from IGF-IGFBP complexes?.
        Growth Horm IGF Res. 2008; 18: 325-334