Abstract
One of the earliest systemic changes in response to tissue damage and inflammation caused by acute insults such as trauma or infection is the rapid synthesis by hepatocytes of a diverse group of blood proteins termed “acute phase reactants”. Among them, the major ones are C-reactive protein (CRP), serum amyloid A protein (SAA) and serum amyloid p component (SAP). In humans and most mammals, the concentrations of CRP and SAA may increase by several thousand-fold in the circulating blood and selectively deposit at sites of damaged tissue. A major function of CRP appears to be the recognition both of infectious agents and of damaged cells and their products. SAA is a member of HDL3 apolipoproteins and thought to inhibit reverse cholesterol transport. SAP is found in all forms of amyloid deposits. SAP responds to acute insults in mice but not in humans. It is a normal constituent of human plasma and tissues. Its association with many ligands and its conservation during evolution imply important functions. However, its physiological role is unclear.
It has been considered that atherosclerosis may be the result of a specialized chronic inflammatory fibroproliferative process; endothelial cells, macrophages, lymphocytes, smooth muscle cells and their cytokines participate in atherosclerotic process, which has become excessive and in its excess this protective response has become the disease state. This hypothesis led us to investigate if the three major acute phase reactants partcipate in human atherosclerosis. Recently, we have reported the presence of CRP and SAP in human aortic atherosclerotic lesions. The aim of this study is to investigate the localization of SAA in the lesions.
Serial sections of paraffin-embedded specimens of atherosclerotic abdominal aorta from autopsied patients, among whom amyloidosis was ruled out, were dewaxed. The one sections were stained with Congo-red to detect amyloid deposit but proved to be negative. The other ones were immunostained by the Streptavidin-Biotin method using a monoclonal anti-human SAA antibody (mcl; Dako) as the primary antibody. As a result, positive staining was observed extracellularly in the necrotic cores of atheromatous plaques, and intracellularly in foam cells. No staining was obtained when the primary antibody was substituted with non-immune mouse serum.
The present study demonstrates that SAA antigen is present in aortic atherosclerotic lesions of patients without amyloidosis. Together with our recent reports, this suggests that the three major acute phase reactants participate in atherosclerosis.
