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Serum amyloid A augments the atherogenic effects of cholesteryl ester transfer protein

Ailing Ji1, Andrea C Trumbauer1, Victoria P Noffsinger1

  • 1Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, USA.

Journal of Lipid Research
|April 2, 2023
PubMed

Insights

Serum amyloid A (SAA) augments the pro-atherosclerotic effects of cholesteryl ester transfer protein (CETP). Deficiency of SAA prevents CETP-driven atherosclerosis, suggesting CETP inhibition benefits patients with high SAA levels.

Area of Science:

  • Cardiovascular Science
  • Immunology
  • Lipid Metabolism

Background:

  • Serum amyloid A (SAA) is a pro-atherogenic protein implicated in cardiovascular disease (CVD).
  • High-density lipoprotein (HDL) normally masks SAA's pro-inflammatory effects.
  • Cholesteryl ester transfer protein (CETP) remodeling of HDL liberates SAA, restoring its pro-atherogenic activity.

Purpose of the Study:

  • To investigate if SAA deficiency suppresses the pro-atherogenic effects of CETP.
  • To determine the role of SAA in CETP-mediated atherosclerosis.

Main Methods:

  • Utilized apolipoprotein E knockout (ApoE-/-) mice and ApoE-/- mice lacking SAA isoforms (SAA-TKO).
  • Adeno-associated virus-mediated expression of CETP was employed in these mouse models.
  • Quantified atherosclerotic lesion area in the aortic arch and analyzed plasma lipids and inflammatory markers.

Main Results:

  • CETP expression significantly increased atherosclerosis in ApoE-/- mice but not in ApoE-/- SAA-TKO mice.
  • No significant effects of CETP or SAA genotype on plasma lipids or inflammatory markers were observed.
  • Increased atherosclerosis in CETP-expressing ApoE-/- mice correlated with elevated SAA in aortic root sections.

Conclusions:

  • SAA significantly augments the atherogenic effects of CETP.
  • Targeting CETP may offer therapeutic benefits for individuals with elevated SAA levels.
  • SAA plays a critical role in mediating CETP-induced atherosclerosis.

Keywords:
HDLapolipoproteinatherosclerosischolesteryl ester transfer proteininflammationlipid metabolismserum amyloid A

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