Abstract
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.
Abbreviations:
DTT (dithiothreitol), FPLC (fast protein liquid chromatography), LPS (lipopolysaccharide), PMA (phorbol-12 myristate 13-acetate), SR-BI (scavenger receptor BI)Keywords
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 accessOne-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:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Structure and function of the pentraxins.Curr. Opin. Immunol. 1995; 7: 54-64
- Pentraxins, humoral innate immunity and tissue injury.Curr. Opin. Immunol. 2008; 20: 538-544
- Structure of pentameric human serum amyloid P component.Nature. 1994; 367: 338-345
- Biology of serum amyloid P component.Ann. N Y Acad. Sci. 1982; 389: 286-298
- Binding of serum amyloid P-component (SAP) by amyloid fibrils.Clin. Exp. Immunol. 1979; 38: 284-293
- Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene.Nat. Med. 1997; 3: 855-859
- 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
- Serum amyloid P component is the major calcium-dependent specific DNA binding protein of the serum.Biochem. Biophys. Res. Commun. 1987; 148: 308-313
- Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity.Nat. Med. 1999; 5: 694-697
- 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
- Characterization of serum amyloid P component from human aortic atherosclerotic lesions.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 252-257
- 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
- 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
- Serum amyloid P colocalizes with apolipoproteins in human atheroma: functional implications.J. Lipid Res. 2007; 48: 2162-2171
- 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
- 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
- Serum amyloid A promotes cholesterol efflux mediated by scavenger receptor B-I.J. Biol. Chem. 2005; 280: 35890-35895
- cAMP induces ABCA1 phosphorylation activity and promotes cholesterol efflux from fibroblasts.J. Lipid Res. 2002; 43: 2087-2094
- Enhanced efflux of cholesterol from ABCA1-expressing macrophages to serum from type IV hypertriglyceridemic subjects.Atherosclerosis. 2003; 171: 287-293
Article info
Publication history
Published online: March 02, 2010
Accepted:
January 28,
2010
Received in revised form:
January 13,
2010
Received:
November 12,
2009
Identification
Copyright
© 2010 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
