リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Gut Microbiota Influence the Development of Abdominal Aortic Aneurysm by Suppressing Macrophage Accumulation in Mice」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Gut Microbiota Influence the Development of Abdominal Aortic Aneurysm by Suppressing Macrophage Accumulation in Mice

Shinohara, Ryohei Nakashima, Hitomi Emoto, Takuo Yamashita, Tomoya Saito, Yoshihiro Yoshida, Naofumi Inoue, Taishi Yamanaka, Katsuhiro Okada, Kenji Hirata, Ken-ichi 神戸大学

2022.12

概要

Background: Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease characterized by dilated abdominal aorta. Immune cells have been shown to contribute to the development of AAA, and that the gut microbiota is associated with numerous diseases, including cardiovascular diseases, by regulating immune systems or metabolic pathways of the host. However, the interaction between the gut microbiota and AAA remains unknown.

Methods: Apolipoprotein E-deficient male mice were fed a high-cholesterol diet and divided into three groups: the control group was maintained under normal water (control group), the oral AVNM group was maintained under drinking water supplemented with ampicillin, vancomycin, neomycin, and metronidazole, and the i.p. AVNM group was injected AVNM intraperitoneally. After 1 week of pretreatment with antibiotics, these mice were administrated Ang II via subcutaneous osmotic pumps for 4 weeks and euthanized to evaluate AAA formation.

Results: Depletion of gut microbiota by oral AVNM ameliorated the incidence of AAAs (control group: 58.9% versus oral AVNM group: 28.6% versus i.p. AVNM group: 75.0%, P = 0.0005) and prevented death due to ruptured aneurysms (control group: 11% versus oral AVNM group: 0% versus i.p. AVNM group: 15%). Oral AVNM suppressed monocyte storage in the spleen, but not in other organs. Despite possessing a higher level of cholesterol, recruitment of monocytes into the suprarenal aorta was suppressed in the oral AVNM group. In AVNM drinking mice, NOD1 ligand, a kind of PRR ligands, increased the development of AAAs and accumulation of macrophages in the aortae.

Conclusions: The gut microbiota plays a critical role in AAA formation. Therefore, regulation of the microbiota or the immune system can be a therapeutic approach for AAA.

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

1. Golledge J. Abdominal aortic aneurysm: update on pathogen- esis and medical treatments. Nat Rev Cardiol. 2019;16:225–242. doi: 10.1038/s41569-018-0114-9

2. Lederle FA, Johnson GR, Wilson SE, Chute EP, Littooy FN, Bandyk D, Krupski WC, Barone GW, Acher CW, Ballard DJ. Prevalence and asso- ciations of abdominal aortic aneurysm detected through screening. Aneu- rysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Group. Ann Intern Med. 1997;126:441–449. doi: 10.7326/0003- 4819-126-6-199703150-00004

3. Tang W, Yao L, Roetker NS, Alonso A, Lutsey PL, Steenson CC, Lederle FA, Hunter DW, Bengtson LG, Guan W. et al. Lifetime risk and risk factors for abdominal aortic aneurysm in a 24-year prospective study: the ARIC study (Atherosclerosis risk in communities). Arterioscler Thromb Vasc Biol. 2016;36:2468–2477. doi: 10.1161/ATVBAHA.116.308147

4. Raffort J, Lareyre F, Clement M, Hassen-Khodja R, Chinetti G, Mallat Z. Monocytes and macrophages in abdominal aortic aneurysm. Nat Rev Car- diol. 2017;14:457–471. doi: 10.1038/nrcardio.2017.52

5. Oliver-Williams C, Sweeting MJ, Turton G, Parkin D, Cooper D, Rodd C, Thompson SG, Earnshaw JJ; Gloucestershire, Swindon Abdominal Aortic Aneurysm Screening P. Lessons learned about prevalence and growth rates of abdominal aortic aneurysms from a 25-year ultrasound population screen- ing programme. Br J Surg. 2018;105:68–74. doi: 10.1002/bjs.10715

6. Powell JT, Brady AR, Brown LC, Fowkes FG, Greenhalgh RM, Ruckley CV, Thompson SG; United Kingdom Small Aneurysm Trial Participants. Long- term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1445–1452. doi: 10.1056/NEJMoa013527

7. Lederle FA, Wilson SE, Johnson GR, Reinke DB, Littooy FN, Acher CW, Ballard DJ, Messina LM, Gordon IL, Chute EP. et al. Immediate repair com- pared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1437–1444. doi: 10.1056/NEJMoa012573

8. Cao P, De Rango P, Verzini F, Parlani G, Romano L, Cieri E, Group CT. Comparison of surveillance versus aortic endografting for small aneurysm repair (CAESAR): results from a randomised trial. Eur J Vasc Endovasc Surg. 2011;41:13–25. doi: 10.1016/j.ejvs.2010.08.026

9. Ouriel K, Clair DG, Kent KC, Zarins CK; Positive Impact of Endovas- cular Options for treating Aneurysms Early (PIVOTAL) Investigators. Endovascular repair compared with surveillance for patients with small abdominal aortic aneurysms. J Vasc Surg. 2010;51:1081–1087. doi: 10.1016/j.jvs.2009.10.113

10. Dale MA, Ruhlman MK, Baxter BT. Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy. Arterioscler Thromb Vasc Biol. 2015;35:1746–1755. doi: 10.1161/ATVBAHA.115.305269

11. Yodoi K, Yamashita T, Sasaki N, Kasahara K, Emoto T, Matsumoto T, Kita T, Sasaki Y, Mizoguchi T, Sparwasser T. et al. Foxp3+ regula- tory T cells play a protective role in angiotensin II-induced aortic aneu- rysm formation in mice. Hypertension. 2015;65:889–895. doi: 10.1161/ HYPERTENSIONAHA.114.04934

12. Hayashi T, Sasaki N, Yamashita T, Mizoguchi T, Emoto T, Amin HZ, Yodoi K, Matsumoto T, Kasahara K, Yoshida N. et al. Ultraviolet B exposure inhib- its Angiotensin II-induced abdominal aortic aneurysm formation in mice by expanding CD4(+)Foxp3(+) regulatory T cells. J Am Heart Assoc. 2017;6:e007024. doi: 10.1161/JAHA.117.007024

13. Kasahara K, Tanoue T, Yamashita T, Yodoi K, Matsumoto T, Emoto T, Mizoguchi T, Hayashi T, Kitano N, Sasaki N. et al. Commensal bac- teria at the crossroad between cholesterol homeostasis and chronic inflammation in atherosclerosis. J Lipid Res. 2017;58:519–528. doi: 10.1194/jlr.M072165

14. Stepankova R, Tonar Z, Bartova J, Nedorost L, Rossman P, Poledne R, Schwarzer M, Tlaskalova-Hogenova H. Absence of microbiota (germ-free conditions) accelerates the atherosclerosis in ApoE-deficient mice fed standard low cholesterol diet. J Atheroscler Thromb. 2010;17:796–804. doi: 10.5551/jat.3285

15. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63. doi: 10.1038/nature09922

16. Emoto T, Yamashita T, Kobayashi T, Sasaki N, Hirota Y, Hayashi T, So A, Kasahara K, Yodoi K, Matsumoto T. et al. Characterization of gut microbiota profiles in coronary artery disease patients using data mining analysis of terminal restriction fragment length polymorphism: gut microbiota could be a diagnostic marker of coronary artery disease. Heart Vessels. 2017;32:39–46. doi: 10.1007/s00380-016-0841-y

17. Yoshida N, Emoto T, Yamashita T, Watanabe H, Hayashi T, Tabata T, Hoshi N, Hatano N, Ozawa G, Sasaki N. et al. Bacteroides vulgatus and bacteroides dorei reduce gut microbial lipopolysaccharide produc- tion and inhibit atherosclerosis. Circulation. 2018;138:2486–2498. doi: 10.1161/CIRCULATIONAHA.118.033714

18. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575–1584. doi: 10.1056/NEJMoa1109400

19. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19:576–585. doi: 10.1038/nm.3145

20. Shikata F, Shimada K, Sato H, Ikedo T, Kuwabara A, Furukawa H, Korai M, Kotoda M, Yokosuka K, Makino H. et al. Potential influences of gut microbi- ota on the formation of intracranial aneurysm. Hypertension. 2019;73:491–496. doi: 10.1161/HYPERTENSIONAHA.118.11804

21. He X, Bai Y, Zhou H, Wu K. Akkermansia muciniphila alters gut microbiota and immune system to improve cardiovascular diseases in murine model. Front Microbiol. 2022;13:906920. doi: 10.3389/fmicb.2022.906920

22. Miyauchi E, Kim SW, Suda W, Kawasumi M, Onawa S, Taguchi-Atarashi N, Morita H, Taylor TD, Hattori M, Ohno H. Gut microorganisms act together to exacerbate inflammation in spinal cords. Nature. 2020;585:102–106. doi: 10.1038/s41586-020-2634-9

23. Ghigliotti G, Barisione C, Garibaldi S, Brunelli C, Palmieri D, Spinella G, Pane B, Spallarossa P, Altieri P, Fabbi P. et al. CD16(+) monocyte subsets are increased in large abdominal aortic aneurysms and are differentially related with circulating and cell-associated biochemical and inflammatory biomarkers. Dis Markers. 2013;34:131–142. doi: 10.1155/2013/836849

24. Jonsson AL, Backhed F. Role of gut microbiota in atherosclerosis. Nat Rev Cardiol. 2017;14:79–87. doi: 10.1038/nrcardio.2016.183

25. Mellak S, Ait-Oufella H, Esposito B, Loyer X, Poirier M, Tedder TF, Tedgui A, Mallat Z, Potteaux S. Angiotensin II mobilizes spleen monocytes to promote the development of abdominal aortic aneurysm in Apoe-/- mice. Arterioscler Thromb Vasc Biol. 2015;35:378–388. doi: 10.1161/ATVBAHA.114.304389

26. Ulndreaj A, Li A, Chen Y, Besla R, Pacheco S, Althagafi MG, Cybulsky MI, Lindsay T, Robbins CS, Byrne JS. Adventitial recruitment of Lyve-1- mac- rophages drives aortic aneurysm in an angiotensin-2-based murine model. Clin Sci (Lond). 2021;135:1295–1309. doi: 10.1042/CS20200963

27. Daugherty A, Cassis LA. Mouse models of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2004;24:429–434. doi: 10.1161/01.ATV. 0000118013.72016.ea

28. Mebius RE, Kraal G. Structure and function of the spleen. Nat Rev Immunol. 2005;5:606–616. doi: 10.1038/nri1669

29. Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P. et al. Identi- fication of splenic reservoir monocytes and their deployment to inflammatory sites. Science. 2009;325:612–616. doi: 10.1126/science.1175202

30. Robbins CS, Chudnovskiy A, Rauch PJ, Figueiredo JL, Iwamoto Y, Gorbatov R, Etzrodt M, Weber GF, Ueno T, van Rooijen N. et al. Extramedullary hematopoie- sis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions. Cir- culation. 2012;125:364–374. doi: 10.1161/CIRCULATIONAHA.111.061986

31. Rubio-Navarro A, Amaro Villalobos JM, Lindholt JS, Buendia I, Egido J, Blanco-Colio LM, Samaniego R, Meilhac O, Michel JB, Martin-Ventura JL. et al. Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm. Int J Cardiol. 2015;201:66–78. doi: 10.1016/j.ijcard.2015.08.053

32. Weaver LK, Minichino D, Biswas C, Chu N, Lee JJ, Bittinger K, Albeituni S, Nichols KE, Behrens EM. Microbiota-dependent signals are required to sus- tain TLR-mediated immune responses. JCI Insight. 2019;4:e124370. doi: 10.1172/jci.insight.124370

33. Kolypetri P, Liu S, Cox LM, Fujiwara M, Raheja R, Ghitza D, Song A, Daatselaar D, Willocq V, Weiner HL. Regulation of splenic monocyte homeo- stasis and function by gut microbial products. iScience. 2021;24:102356. doi: 10.1016/j.isci.2021.102356

参考文献をもっと見る