Adipocyte-Derived Serum Amyloid A Promotes Angiotensin II-Induced Abdominal Aortic Aneurysms in Obese C57BL/6J Mice

Preetha Shridas, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Steve W. Leung, Adam J. Dugan, Sean E. Thatcher, Lisa A. Cassis, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Obesity increases the risk for human abdominal aortic aneurysms (AAAs) and enhances Ang II (angiotensin II)-induced AAA formation in C57BL/6J mice. Obesity is also associated with increases in perivascular fat that expresses proinflammatory markers including SAA (serum amyloid A). We previously reported that deficiency of SAA significantly reduces Ang II-induced inflammation and AAA in hyperlipidemic apoE-deficient mice. In this study. we investigated whether adipose tissue-derived SAA plays a role in Ang II-induced AAA in obese C57BL/6J mice. Methods: The development of AAA was compared between male C57BL/6J mice (wild type), C57BL/6J mice lacking SAA1.1, SAA2.1, and SAA3 (TKO); and TKO mice harboring a doxycycline-inducible, adipocyte-specific SAA1.1 transgene (TKO-Tgfat; SAA expressed only in fat). All mice were fed an obesogenic diet and doxycycline to induce SAA transgene expression and infused with Ang II to induce AAA. Results: In response to Ang II infusion, SAA expression was significantly increased in perivascular fat of obese C57BL/6J mice. Maximal luminal diameters of the abdominal aorta were determined by ultrasound before and after Ang II infusion, which indicated a significant increase in aortic luminal diameters in wild type and TKO-TGfatmice but not in TKO mice. Adipocyte-specific SAA expression was associated with MMP (matrix metalloproteinase) activity and macrophage infiltration in abdominal aortas of Ang II-infused obese mice. Conclusions: We demonstrate for the first time that SAA deficiency protects obese C57BL/6J mice from Ang II-induced AAA. SAA expression only in adipocytes is sufficient to cause AAA in obese mice infused with Ang II.

Original languageEnglish
Pages (from-to)632-643
Number of pages12
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume42
Issue number5
DOIs
StatePublished - May 1 2022

Bibliographical note

Funding Information:
This work was supported by Department of Veterans Affairs BX004275 (to L.R. Tannock), National Institutes of Health Grants HL134731 (to N.R. Webb and F.C. de Beer) and HL147381 (to L.R. Tannock and P. Shridas), and Washington University Diabetes Research Center Collaborative Pilot and Feasibility Grant DK020579-42 (to P. Shridas). The studies were supported with resources and facilities provided by the Centers of Biomedical Research Excellence (COBRE) at the University of Kentucky, which was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P30 GM127211.

Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.

Keywords

  • adipose tissue
  • aortic aneurysm
  • inflammation
  • obesity
  • serum amyloid A

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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