Age-associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE

Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Pub., c2002-

Monocytes*/metabolism ; Atherosclerosis*/metabolism; Animals ; Mice ; Chemotaxis ; Inflammation/metabolism ; Adipose Tissue/metabolism ; Inflammation Mediators/metabolism ; Mice, Inbred C57BL

Although aging enhances atherosclerosis, we do not know if this occurs via alterations in circulating immune cells, lipid metabolism, vasculature, or adipose tissue. Here, we examined whether aging exerts a direct pro-atherogenic effect on adipose tissue in mice. After demonstrating that aging augmented the inflammatory profile of visceral but not subcutaneous adipose tissue, we transplanted visceral fat from young or aged mice onto the right carotid artery of Ldlr ^-/- recipients. Aged fat transplants not only increased atherosclerotic plaque size with increased macrophage numbers in the adjacent carotid artery, but also in distal vascular territories, indicating that aging of the adipose tissue enhances atherosclerosis via secreted factors. By depleting macrophages from the visceral fat, we identified that adipose tissue macrophages are major contributors of the secreted factors. To identify these inflammatory factors, we found that aged fat transplants secreted increased levels of the inflammatory mediators TNFα, CXCL2, and CCL2, which synergized to promote monocyte chemotaxis. Importantly, the combined blockade of these inflammatory mediators impeded the ability of aged fat transplants to enhance atherosclerosis. In conclusion, our study reveals that aging enhances atherosclerosis via increased inflammation of visceral fat. Our study suggests that future therapies targeting the visceral fat may reduce atherosclerosis disease burden in the expanding older population.
(© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

J Cardiovasc Transl Res. 2019 Oct;12(5):415-424. (PMID: 30835048)
Cell Metab. 2007 Dec;6(6):446-57. (PMID: 18054314)
Nat Med. 2018 Aug;24(8):1246-1256. (PMID: 29988130)
Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1180-1193. (PMID: 28473444)
Int J Mol Sci. 2019 Dec 31;21(1):. (PMID: 31906225)
Circ Res. 2020 Jan 31;126(3):298-314. (PMID: 31818196)
J Clin Invest. 2007 Jan;117(1):185-94. (PMID: 17200718)
Aging (Albany NY). 2012 Dec;4(12):859-60. (PMID: 23363767)
J Immunol Methods. 1994 Sep 14;174(1-2):5-19. (PMID: 8083537)
Atherosclerosis. 2019 Feb;281:31-37. (PMID: 30654169)
Immunology. 2018 Dec;155(4):407-417. (PMID: 30229891)
Nat Protoc. 2009;4(12):1798-806. (PMID: 20010931)
Biochem Biophys Res Commun. 2000 Sep 24;276(2):791-6. (PMID: 11027549)
J Immunol. 2011 Dec 15;187(12):6208-16. (PMID: 22075699)
Atherosclerosis. 1987 Dec;68(3):231-40. (PMID: 3426656)
Cell. 2013 Jun 6;153(6):1194-217. (PMID: 23746838)
Aging Cell. 2010 Oct;9(5):667-84. (PMID: 20701600)
EBioMedicine. 2017 Jul;21:21-28. (PMID: 28416161)
Aging Cell. 2019 Jun;18(3):e12950. (PMID: 30907060)
Biology (Basel). 2019 Apr 11;8(2):. (PMID: 30978929)
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13531-6. (PMID: 14581613)
Arterioscler Thromb Vasc Biol. 2017 Sep;37(9):e131-e157. (PMID: 28729366)
Circulation. 2008 Apr 1;117(13):1649-57. (PMID: 18347211)
Nat Rev Immunol. 2013 Oct;13(10):709-21. (PMID: 23995626)
Nat Commun. 2020 May 5;11(1):2202. (PMID: 32371953)
Aging Cell. 2023 Feb;22(2):e13783. (PMID: 36683460)
Aging Cell. 2016 Oct;15(5):973-7. (PMID: 26864908)
Circ Res. 2012 Jul 6;111(2):245-59. (PMID: 22773427)
Nat Rev Immunol. 2013 Dec;13(12):875-87. (PMID: 24157572)
Diabetes Metab J. 2019 Jun;43(3):247-256. (PMID: 30968618)
J Immunol. 2012 Apr 15;188(8):3603-10. (PMID: 22442444)
Nat Med. 2013 Sep;19(9):1166-72. (PMID: 23933982)
J Clin Invest. 2013 Mar;123(3):966-72. (PMID: 23454759)
Mech Ageing Dev. 2021 Dec;200:111598. (PMID: 34762939)
Aging Cell. 2007 Aug;6(4):565-75. (PMID: 17578509)
Diabetes. 2007 Jan;56(1):16-23. (PMID: 17192460)
Leukemia. 2002 Oct;16(10):2142-7. (PMID: 12357369)
Nat Rev Cardiol. 2021 Jan;18(1):58-68. (PMID: 32918047)
J Am Heart Assoc. 2017 Oct 27;6(11):. (PMID: 29079564)
Nature. 2017 Oct 5;550(7674):119-123. (PMID: 28953873)
Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):E6301-10. (PMID: 26578790)
Semin Immunopathol. 2020 Oct;42(5):545-557. (PMID: 32747977)
Arterioscler Thromb Vasc Biol. 2014 Aug;34(8):1723-30. (PMID: 24947528)
JAMA. 2012 Feb 1;307(5):491-7. (PMID: 22253363)
Aging (Albany NY). 2019 Oct 23;11(20):8730-8732. (PMID: 31645481)
Cell Metab. 2013 Oct 1;18(4):519-32. (PMID: 24093676)
J Biol Chem. 2015 May 22;290(21):13250-62. (PMID: 25869128)
J Leukoc Biol. 2021 Apr;109(4):777-791. (PMID: 32881070)
Nat Cell Biol. 2008 Sep;10(9):1027-38. (PMID: 19160483)
Gerontology. 2020;66(2):114-121. (PMID: 31412335)
Immunol Lett. 2007 Oct 15;112(2):61-7. (PMID: 17719095)
Mucosal Immunol. 2019 Mar;12(2):545-554. (PMID: 30617300)
Atherosclerosis. 2011 Nov;219(1):33-9. (PMID: 21835408)
Cell. 2019 Jul 25;178(3):686-698.e14. (PMID: 31257031)
Immunity. 2020 Sep 15;53(3):510-523. (PMID: 32937152)
Mol Metab. 2014 Jul 10;3(6):664-75. (PMID: 25161889)
Clin Sci (Lond). 2020 Jan 31;134(2):315-330. (PMID: 31998947)
Circ Res. 2018 Sep 14;123(7):849-867. (PMID: 30355080)
J Clin Invest. 2017 Jan 3;127(1):5-13. (PMID: 28045397)
J Cell Biochem. 2009 Dec 15;108(6):1233-43. (PMID: 19798678)
Arterioscler Thromb Vasc Biol. 2017 Dec;37(12):2322-2332. (PMID: 28970293)
Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1412-8. (PMID: 19759373)
Cell Death Dis. 2022 Apr 4;13(4):300. (PMID: 35379822)

R01 AG028082 United States AG NIA NIH HHS; R01 AI138347 United States AI NIAID NIH HHS; R35 HL155169 United States HL NHLBI NIH HHS; T32 AG062403 United States AG NIA NIH HHS

Keywords: atherosclerosis; inflammation; macrophage; monocyte; visceral adipose tissue

0 (Inflammation Mediators)

Date Created: 20230123 Date Completed: 20230215 Latest Revision: 20240202

20240202

PMC9924943

10.1111/acel.13783

36683460