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Published on: October 12, 2017
Serum amyloid A3 is pro-atherogenic.
Joel C Thompson1, Patricia G Wilson1, Preetha Shridas2
1Department 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.
Serum amyloid A3 (SAA3) significantly increases atherosclerosis in mice. This finding resolves a paradox and supports the role of SAA in cardiovascular disease development.
Area of Science:
- Cardiovascular biology
- Immunology
- Molecular medicine
Background:
- Serum amyloid A (SAA) is linked to cardiovascular events.
- Murine SAA isoforms SAA1.1 and SAA2.1 deficiency do not impact atherosclerosis.
- SAA3 is an expressed acute phase isoform in mice, unlike in humans.
Purpose of the Study:
- To investigate the role of SAA3 in atherosclerosis development in mice.
- To determine if SAA3 exacerbates or ameliorates atherosclerosis.
Main Methods:
- ApoE knockout mice were utilized as the atherosclerosis model.
- Adeno-associated virus mediated SAA3 overexpression.
- Anti-sense oligonucleotide approach was used for SAA3 suppression.
Main Results:
- SAA3 overexpression resulted in a 4-fold increase in atherosclerosis lesion area.
- SAA3 suppression significantly decreased atherosclerosis in SAA1.1/SAA2.1 deficient mice.
- Statistical significance was observed for both overexpression (p=0.01) and suppression (p<0.0001) studies.
Conclusions:
- SAA3 plays a pro-atherogenic role in mice.
- These findings reconcile existing literature and support epidemiological data on SAA and atherosclerosis.
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