A brief elevation of serum amyloid A is sufficient to increase atherosclerosis.

Serum Amyloid A (SAA) has a number of pro-atherogenic effects including induction of vascular proteoglycans. Chronically elevated SAA was recently shown to increase atherosclerosis in mice. The purpose of this study was to determine if a brief increase in SAA similarly increased atherosclerosis in a murine model. rag1-/- x apoe-/- and apoe-/- male mice were injected, multiple times or just once respectfully, with an adenoviral vector encoding human SAA1 (ad-SAA), or controls and maintained on chow for 12-16 weeks. Mice receiving multiple injections of ad-SAA, in which SAA elevation was sustained, had increased atherosclerosis compared to controls. Strikingly, mice receiving only a single injection of ad-SAA, in which SAA was only briefly elevated, also had increased atherosclerosis compared to controls. Using in vitro studies we demonstrate that SAA treatment leads to increased LDL retention, and that prevention of TGF-β signaling prevents SAA induced increases in LDL retention and SAA induced increases in vascular biglycan content. We propose that SAA increases atherosclerosis development via induction of TGF-β, increased vascular biglycan content and increased LDL retention. These data suggest that even short term inflammation, as seen in intensive hospitalization may increase the risk of developing cardiovascular disease in an SAA dependent manner.