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Atherosclerosis. 2018 Jan;268:32-35. doi: 10.1016/j.atherosclerosis.2017.11.011. Epub 2017 Nov 17.

Serum amyloid A3 is pro-atherogenic.

Author information

1
Department of Veterans Affairs, Lexington, KY 40502, USA; Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA; Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, 40536, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, 40536, USA.
2
Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA; Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, 40536, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, 40536, USA.
3
Department of Physiology, University of Kentucky, Lexington, KY, 40536, USA; Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, 40536, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, 40536, USA.
4
Department of Veterans Affairs, Lexington, KY 40502, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, 40536, USA; Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, 40536, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, 40536, USA.
5
Department of Veterans Affairs, Lexington, KY 40502, USA; Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA; Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, 40536, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, 40536, USA. Electronic address: lisa.tannock@uky.edu.

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.

KEYWORDS:

Atherosclerosis; Inflammation; Murine models

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