Abstract
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.
Document Type
Article
Publication Date
5-2023
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.jlr.2023.100365
Funding Information
This work was supported by the National Institutes of Health grants HL134731 (to N. R. W. and F. D.) and HL147381 (to L. T. and P. S.), Department of Veterans Affairs BX004275 (to L. T.), Washington University Diabetes Research Center Collaborative Pilot and Feasibility Grant DK020579-42 (to P. S.).
Repository Citation
Ji, Ailing; Trumbauer, Andrea C.; Noffsinger, Victoria P.; de Beer, Frederick C.; Webb, Nancy R.; Tannock, Lisa R.; and Shridas, Preetha, "Serum amyloid A augments the atherogenic effects of cholesteryl ester transfer protein" (2023). Saha Cardiovascular Research Center Faculty Publications. 65.
https://uknowledge.uky.edu/cvrc_facpub/65
Included in
Biochemistry Commons, Cardiology Commons, Cell Biology Commons, Circulatory and Respiratory Physiology Commons, Endocrinology Commons
Notes/Citation Information
© 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).