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Serum amyloid A3 is pro-atherogenic.

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.

SUBMITTER: Thompson JC

PROVIDER: S-EPMC5839639 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Serum amyloid A3 is pro-atherogenic.

Thompson Joel C JC Wilson Patricia G PG Shridas Preetha P Ji Ailing A de Beer Maria M de Beer Frederick C FC Webb Nancy R NR Tannock Lisa R LR

Atherosclerosis 20171117

<h4>Background and aims</h4>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.<h4>Methods</h4>ApoE<sup>-/-</sup> mice were used as the model for all studies. ...[more]

PMID: 29175652

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