April 21, 2023
Serum Amyloid A augments the atherogenic effects of Cholesteryl Ester Transfer Protein
Originally Published on March 31, 2023: https://www.sciencedirect.com/science/article/pii/S002222752300038X?via%3Dihub
Authors: Ailing Ji, Andrea C Trumbauer, Victoria P Noffsinger, Frederick C de Beer, Nancy R Webb, Lisa R Tannock, Preetha Shridas
Serum Amyloid A (SAA) is predictive of cardiovascular disease (CVD) in humans and causes atherosclerosis in mice. SAA has many pro-atherogenic effects in vitro. However, HDL, the major carrier of SAA in the circulation, masks these effects. The remodeling of HDL by CETP liberates SAA restoring its pro-inflammatory activity. Here, we investigated whether deficiency of SAA suppresses the previously described pro-atherogenic effect of Cholesteryl Ester Transfer Protein (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 AAV-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.