Serum amyloid A3 is pro-atherogenic. (January 2018)

• Record Type: Journal Article
• Authors: Thompson, Joel C.; Wilson, Patricia G.; Shridas, Preetha; Ji, Ailing; de Beer, Maria; de Beer, Frederick C.; Webb, Nancy R.; Tannock, Lisa R.
• Is Part Of: Atherosclerosis. Volume 268(2018)
• Page Start: 32
• Page End: 35
• Publication Date: 2018-01
• Subjects: Inflammation -- Atherosclerosis -- Murine models; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2017.11.011
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: Serum amyloid A (SAA) predicts cardiovascular events. Overexpression of SAA increases atherosclerosis development; however, deficiency of two of the murine acute phase isoforms, SAA1.1 and SAA2.1, has no effect on atherosclerosis. SAA3 is a pseudogene in humans, but is an expressed acute phase isoform in mice. The goal of this study was to determine if SAA3 affects atherosclerosis in mice. Methods: ApoE -/- mice were used as the model for all studies. SAA3 was overexpressed by an adeno-associated virus or suppressed using an anti-sense oligonucleotide approach. Results: Over-expression of SAA3 led to a 4-fold increase in atherosclerosis lesion area compared to control mice ( p = 0.01). Suppression of SAA3 decreased atherosclerosis in mice genetically deficient in SAA1.1 and SAA2.1 ( p < 0.0001). Conclusions: SAA3 augments atherosclerosis in mice. Our results resolve a previous paradox in the literature and support extensive epidemiological data that SAA is pro-atherogenic. Highlights: Increased expression of SAA3 increases atherosclerosis development. Suppression of SAA3 in mice deficient in SAA1.1 and SAA2.1 attenuates atherosclerosis development. SAA3 has pro-atherogenic activity in mice.