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Adipocyte-Derived Serum Amyloid A Promotes Angiotensin II-Induced Abdominal Aortic Aneurysms in Obese C57BL/6J Mice.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2022 May; Vol. 42 (5), pp. 632-643. Date of Electronic Publication: 2022 Mar 28. - Publication Year :
- 2022
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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.<br />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 <superscript>fat</superscript> ; 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.<br />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-TG <superscript>fat</superscript> 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.<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 42
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 35344382
- Full Text :
- https://doi.org/10.1161/ATVBAHA.121.317225