A brief elevation of serum amyloid A is suffi cient to increase atherosclerosis

Joel C. Thompson, Colton Jayne, Jennifer Thompson, Patricia G. Wilson, Meghan H. Yoder, Nancy Webb, Lisa R. Tannock

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Serum amyloid A (SAA) has a number of proatherogenic effects including induction of vascular proteoglycans. Chronically elevated SAA was recently shown to increase atherosclerosis in mice. The purpose of this study was to determine whether a brief increase in SAA similarly increased atherosclerosis in a murine model. The recombination activating gene 1-defi cient ( rag1 ) × apolipoprotein E-defi cient ( apoe ) and apoe male mice were injected, multiple times or just once respectively, with an adenoviral vector encoding human SAA1 (ad-SAA); the injected mice and controls were maintained on chow for 12-16 weeks. Mice receiving multiple injections of ad-SAA, in which SAA elevation was sustained, had increased atherosclerosis compared with controls. Strikingly, mice receiving only a single injection of ad-SAA, in which SAA was only briefl y elevated, also had increased atherosclerosis compared with controls. Using in vitro studies, we demonstrate that SAA treatment leads to increased LDL retention, and that prevention of transforming growth factor beta (TGF-) signaling prevents SAA-induced increases in LDL retention and SAAinduced increases in vascular biglycan content. We propose that SAA increases atherosclerosis development via induction of TGF-, increased vascular biglycan content, and increased LDL retention. These data suggest that even short-term infl ammation with concomitant increase in SAA may increase the risk of developing CVD.

Original languageEnglish
Pages (from-to)286-293
Number of pages8
JournalJournal of Lipid Research
Volume56
Issue number2
DOIs
StatePublished - Feb 1 2015

Keywords

  • Apolipoproteins
  • Cardiovascular Disease
  • Extracellular Matrix
  • Free-Form: Biglycan
  • Lipoproteins
  • Proteoglycans
  • Transforming Growth Factor Beta
  • Vascular Biology

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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