Serum amyloid A augments the atherogenic effects of cholesteryl ester transfer protein

• Published in: Journal of Lipid Research
• Main Authors: Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Frederick C. de Beer, Nancy R. Webb, Lisa R. Tannock, Preetha Shridas
• Format: Article
• Language: English
• Published: Elsevier 2023-05-01
• Subjects: serum amyloid A; cholesteryl ester transfer protein; atherosclerosis; lipid metabolism; apolipoprotein; HDL
• Online Access: http://www.sciencedirect.com/science/article/pii/S002222752300038X

Serum amyloid A (SAA) is predictive of CVD in humans and causes atherosclerosis in mice. SAA has many proatherogenic effects in vitro. However, HDL, the major carrier of SAA in the circulation, masks these effects. The remodeling of HDL by cholesteryl ester transfer protein (CETP) liberates SAA restoring its proinflammatory activity. Here, we investigated whether deficiency of SAA suppresses the previously described proatherogenic effect of CETP. ApoE−/− mice and apoE−/− mice deficient in the three acute-phase isoforms of SAA (SAA1.1, SAA2.1, and SAA3; “apoE−/− SAA-TKO”) with and without adeno-associated virus-mediated expression of CETP were studied. There was no effect of CETP expression or SAA genotype on plasma lipids or inflammatory markers. Atherosclerotic lesion area in the aortic arch of apoE−/− mice was 5.9 ± 1.2%; CETP expression significantly increased atherosclerosis in apoE−/− mice (13.1 ± 2.2%). However, atherosclerotic lesion area in the aortic arch of apoE−/− SAA-TKO mice (5.1 ± 1.1%) was not significantly increased by CETP expression (6.2 ± 0.9%). The increased atherosclerosis in apoE−/− mice expressing CETP was associated with markedly increased SAA immunostaining in aortic root sections. Thus, SAA augments the atherogenic effects of CETP, which suggests that inhibiting CETP may be of particular benefit in patients with high SAA.