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

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: Amyloid P component, Pentraxin, HDL, Cardiovascular disease, Cholesterol efflux, Scavenger receptor BI, ABCA1