Serum Amyloid A and Lipoprotein Retention in Murine Models of Atherosclerosis

K. D. O'Brien
2005 Arteriosclerosis, Thrombosis and Vascular Biology  
Objective-Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk in humans. Because SAA associates primarily with lipoproteins in plasma and has proteoglycan binding domains, we postulated that SAA might mediate lipoprotein retention on atherosclerotic extracellular matrix. Methods and Results-Immunohistochemistry was performed for SAA, apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and perlecan on proximal aortic lesions from chow-fed low-density
more » ... ein receptor (LDLR) Ϫ/Ϫ and apoE Ϫ/Ϫ mice euthanized at 10, 50, and 70 weeks. SAA was detected on atherosclerotic lesion extracellular matrix at all time points in both strains. SAA area correlated highly with lesion areas ( apoE Ϫ/Ϫ , rϭ0.76; LDLR Ϫ/Ϫ , rϭ0.86), apoA-I areas (apoE Ϫ/Ϫ , rϭ0.88; LDLR Ϫ/Ϫ , rϭ0.80), apoB areas (apoE Ϫ/Ϫ , rϭ0.74; LDLR Ϫ/Ϫ , rϭ0.89), and perlecan areas (apoE Ϫ/Ϫ , rϭ0.83; LDLR Ϫ/Ϫ , rϭ0.79) (all PϽ0.0001). In vitro, SAA enrichment increased high-density lipoprotein (HDL) binding to heparan sulfate proteoglycans, and immunoprecipitation experiments using plasma from apoE Ϫ/Ϫ and LDLR Ϫ/Ϫ mice demonstrated that SAA was present on both apoA-I-containing and apoB-containing lipoproteins. Conclusions-In chow-fed apoE Ϫ/Ϫ and LDLR Ϫ/Ϫ mice, SAA is deposited in murine atherosclerosis at all stages of lesion development, and SAA immunoreactive area correlates highly with lesion area, apoA-I area, apoB area, and perlecan area. These findings are consistent with a possible role for SAA-mediated lipoprotein retention in atherosclerosis. (Arterioscler Thromb Vasc Biol. 2005;25:785-790.)
doi:10.1161/01.atv.0000158383.65277.2b pmid:15692094 fatcat:w3gqswr5pzalbom2gybst7bzfu