Serum amyloid A3 is pro-atherogenic

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Aorta / metabolism*
  • Aorta / pathology
  • Aortic Diseases / blood*
  • Aortic Diseases / diagnosis
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control
  • Atherosclerosis / blood*
  • Atherosclerosis / genetics
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control
  • Disease Models, Animal
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Plaque, Atherosclerotic*
  • Serum Amyloid A Protein / deficiency
  • Serum Amyloid A Protein / genetics
  • Serum Amyloid A Protein / metabolism*

Substances

  • Saa3 protein, mouse
  • Serum Amyloid A Protein