Research Article| Volume 211, ISSUE 1, P90-95, July 2010

Download started.


Accumulation and expression of serum amyloid P component in human atherosclerotic lesions


      Serum amyloid P component (SAP) is a member of pentraxins. Previous studies indicate that SAP exists in human atherosclerotic aortic intima and the plasma SAP levels are associated with cardiovascular disease. In this study, we characterized SAP in normal and atherosclerotic intima, investigated the source of SAP in atherosclerotic lesions, and assessed the effect of SAP on HDL function. Immunohistochemical staining and electroimmunoassay indicated that SAP is not present in normal aortic intima which excludes the possibility that SAP non-specifically deposits in aortic intima via its binding to microfibrils. Notably, SAP levels are correlated with the severity of atherosclerotic lesions. Fast protein liquid chromatography (FPLC) and Western blot analysis revealed that SAP exists in atherosclerotic lesions in multiple forms. Soluble SAP accumulates in the lesions as decamer in free or bound forms via ligand-binding to its ligand(s). Insoluble SAP accumulates in the lesions in covalent-bound forms conjugated to collagen/collagen-like substances via disulfide (–S–S–) bonds. In situ hybridization and RT-PCR analysis revealed that SAP is generated in atherosclerotic lesions, at least partly, by macrophages and smooth muscle cells in neointima. Functional analysis demonstrated that SAP associated with HDL promotes SR-BI-dependent cholesterol efflux and lipid-free SAP enhances ABCA1-dependent cholesterol efflux. In conclusion, our findings demonstrate that SAP is specifically accumulated and expressed in atherosclerotic lesions. SAP may be involved in cholesterol clearance through its role in promoting cholesterol efflux.


      DTT (dithiothreitol), FPLC (fast protein liquid chromatography), LPS (lipopolysaccharide), PMA (phorbol-12 myristate 13-acetate), SR-BI (scavenger receptor BI)


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Gewurz H.
        • Zhang X.-H.
        • Lint T.F.
        Structure and function of the pentraxins.
        Curr. Opin. Immunol. 1995; 7: 54-64
        • Manfredi A.A.
        • Rovere-Querini P.
        • Bottazzi B.
        • Garlanda C.
        • Mantovani A.
        Pentraxins, humoral innate immunity and tissue injury.
        Curr. Opin. Immunol. 2008; 20: 538-544
        • Emsley J.
        • White H.E.
        • O’Hara B.P.
        • et al.
        Structure of pentameric human serum amyloid P component.
        Nature. 1994; 367: 338-345
        • Pepys M.B.
        • Baltz M.L.
        • de Beer F.C.
        • et al.
        Biology of serum amyloid P component.
        Ann. N Y Acad. Sci. 1982; 389: 286-298
        • Pepys M.B.
        • Dyck R.F.
        • de Beer F.C.
        • Skinner M.
        • Cohen A.S.
        Binding of serum amyloid P-component (SAP) by amyloid fibrils.
        Clin. Exp. Immunol. 1979; 38: 284-293
        • Botto M.
        • Hawkins P.N.
        • Bickerstaff M.C.
        • et al.
        Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene.
        Nat. Med. 1997; 3: 855-859
        • Breathnach S.M.
        • Kofler H.
        • Sepp N.
        • et al.
        Serum amyloid P component binds to cell nuclei in vitro and to in vivo deposits of extracellular chromatin in systemic lupus erythematosus.
        J. Exp. Med. 1989; 170: 1433-1438
        • Pepys M.B.
        • Butler P.J.
        Serum amyloid P component is the major calcium-dependent specific DNA binding protein of the serum.
        Biochem. Biophys. Res. Commun. 1987; 148: 308-313
        • Bickerstaff M.C.
        • Botto M.
        • Hutchinson W.L.
        • et al.
        Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity.
        Nat. Med. 1999; 5: 694-697
        • Buckley D.I.
        • Fu R.
        • Freeman M.
        • Rogers K.
        • Helfand M.
        C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force.
        Ann. Intern. Med. 2009; 151: 483-495
        • Li X.A.
        • Hatanaka K.
        • Ishibashi-Ueda H.
        • Yutani C.
        • Yamamoto A.
        Characterization of serum amyloid P component from human aortic atherosclerotic lesions.
        Arterioscler. Thromb. Vasc. Biol. 1995; 15: 252-257
        • Li X.A.
        • Yutani C.
        • Shimokado K.
        Serum amyloid P component associates with high density lipoprotein as well as very low density lipoprotein but not with low density lipoprotein.
        Biochem. Biophys. Res. Commun. 1998; 244: 249-252
        • Jenny N.S.
        • Arnold A.M.
        • Kuller L.H.
        • Tracy R.P.
        • Psaty B.M.
        Serum amyloid P and cardiovascular disease in older men and women: results from the Cardiovascular Health Study.
        Arterioscler. Thromb. Vasc. Biol. 2007; 27: 352-358
        • Stewart C.R.
        • Haw III, A.
        • Lopez R.
        • et al.
        Serum amyloid P colocalizes with apolipoproteins in human atheroma: functional implications.
        J. Lipid Res. 2007; 48: 2162-2171
        • Stary H.C.
        • Chandler A.B.
        • Dinsmore R.E.
        • et al.
        A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.
        Circulation. 1995; 92: 1355-1374
        • Sato M.
        • Sugano N.
        • Ohzono K.
        • et al.
        Apoptosis and expression of stress protein (ORP150, HO1) during development of ischaemic osteonecrosis in the rat.
        J. Bone Joint Surg. Br. 2001; 83-B: 751-759
        • van der Westhuyzen D.R.
        • Cai L.
        • de Beer M.C.
        • de Beer F.C.
        Serum amyloid A promotes cholesterol efflux mediated by scavenger receptor B-I.
        J. Biol. Chem. 2005; 280: 35890-35895
        • Haidar B.
        • Denis M.
        • Krimbou L.
        • Marcil M.
        • Genest Jr., J.
        cAMP induces ABCA1 phosphorylation activity and promotes cholesterol efflux from fibroblasts.
        J. Lipid Res. 2002; 43: 2087-2094
        • Fournier N.
        • Francone O.
        • Rothblat G.
        • et al.
        Enhanced efflux of cholesterol from ABCA1-expressing macrophages to serum from type IV hypertriglyceridemic subjects.
        Atherosclerosis. 2003; 171: 287-293