Serum amyloid P co-localizes with apolipoproteins in human atheroma: Functional implications

Cameron R. Stewart, Antonio Haw, Roland Lopez, Thomas O. McDonald, Judy M. Callaghan, Malcolm J. McConville, Kathryn J. Moore, Geoffrey J. Howlett, and Kevin D. O'Brien

Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Victoria 3010

Corresponding Author: ghowlett{at}unimelb.edu.au

Serum amyloid P (SAP) is a common component of human amyloid deposits, and has been identified in atherosclerotic lesions. We investigated the extent of the co-localization of SAP with apolipoproteins A-I, B, C-II and E in human coronary arteries, and explored potential roles for SAP in these regions; specifically, the effect of SAP on the rate of formation and macrophage recognition of amyloid fibrils composed of apolipoprotein (apo) C-II. Analysis of 42 human arterial sections by immunohistochemistry and double label fluorescence microscopy demonstrated that SAP and apoA-I, B, C-II and E were significantly elevated in atherosclerotic lesions compared to non-atherosclerotic segments. SAP co-localized with all four apolipoproteins to a similar extent, whereas plaque macrophages were found to correlate most strongly with apoC-II and apoB. In vitro studies showed that SAP accelerated the formation of amyloid fibrils by purified apoC-II. Furthermore, SAP strongly inhibited phagocytosis of apoC-II amyloid fibrils by primary macrophages and macrophage cell lines, and blocked the resultant production of reactive oxygen species. The ability of SAP to accelerate apoC-II amyloid fibril formation and inhibit macrophage recognition of apoC-II fibrils suggests that SAP may modulate the inflammatory response to amyloid fibrils in atherosclerosis.

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