1. Adipocyte-Derived Serum Amyloid A Promotes Angiotensin II-Induced Abdominal Aortic Aneurysms in Obese C57BL/6J Mice.
- Author
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Shridas P, Ji A, Trumbauer AC, Noffsinger VP, Leung SW, Dugan AJ, Thatcher SE, Cassis LA, de Beer FC, Webb NR, and Tannock LR
- Subjects
- Adipocytes metabolism, Animals, Apolipoproteins E genetics, Disease Models, Animal, Doxycycline adverse effects, Male, Matrix Metalloproteinases, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Obese, Obesity complications, Serum Amyloid A Protein genetics, Serum Amyloid A Protein metabolism, Angiotensin II pharmacology, Aortic Aneurysm, Abdominal chemically induced, Aortic Aneurysm, Abdominal genetics
- 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-Tg
fat ; 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-TGfat mice 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.- Published
- 2022
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