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Published in: BMC Cardiovascular Disorders 1/2024

Open Access 01-12-2024 | Aortic Aneurysm | Research

The causal relationship between thoracic aortic aneurysm and immune cells: a mendelian randomization study

Authors: Guoli Liu, Sha Pan, Hongli Xia, Mincai Li, Ansen Wu

Published in: BMC Cardiovascular Disorders | Issue 1/2024

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Abstract

One of the pathogenic causes of thoracic aortic aneurysm (TAA), a dangerous vascular condition that can cause aortic rupture, is autoimmune disorders. Currently, immune cell clustering is becoming more and more refined, and the specific immune cell phenotypes involved are yet unknown. Here, we want to clarify the causal link between TAA risk and 731 immune cell traits. There was a Mendelian randomization analysis (MR). We discovered that the presence of TAA led to an increase in CD45 on CD33 HLA-DR myeloid cells, an increase in CD45 on natural killer cells, and a decrease in FSC-A on granulocytes after applying FDR correction. Our research also revealed a strong correlation between the incidence of TAA and an increase in immune cells with CD3 on CD39+ CD4+, and CD25 on IgD CD27 phenotypes. Through genetic techniques, our research has shown the intimate relationship between immune cells and TAA, offering direction for future clinical investigations.
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Literature
1.
go back to reference Salameh MJ, Black JH 3rd, Ratchford EV. Thoracic aortic aneurysm. Vasc Med. 2018;23(6):573–8. Salameh MJ, Black JH 3rd, Ratchford EV. Thoracic aortic aneurysm. Vasc Med. 2018;23(6):573–8.
2.
go back to reference Rega S, Farina F, Bouhuis S, de Donato S, Chiesa M, Poggio P, Cavallotti L, Bonalumi G, Giambuzzi I, Pompilio G, et al. Multi-omics in thoracic aortic aneurysm: the complex road to the simplification. Cell Biosci. 2023;13(1):131.CrossRefPubMedPubMedCentral Rega S, Farina F, Bouhuis S, de Donato S, Chiesa M, Poggio P, Cavallotti L, Bonalumi G, Giambuzzi I, Pompilio G, et al. Multi-omics in thoracic aortic aneurysm: the complex road to the simplification. Cell Biosci. 2023;13(1):131.CrossRefPubMedPubMedCentral
3.
go back to reference Papakonstantinou NA, Rorris FP. Elective replacement of the ascending aorta: is the 5.5-cm threshold appropriate? The insidious, small aorta. Eur J Cardiothorac Surg. 2021;59(3):554–61.CrossRefPubMed Papakonstantinou NA, Rorris FP. Elective replacement of the ascending aorta: is the 5.5-cm threshold appropriate? The insidious, small aorta. Eur J Cardiothorac Surg. 2021;59(3):554–61.CrossRefPubMed
4.
go back to reference Folkersen L, Wagsater D, Paloschi V, Jackson V, Petrini J, Kurtovic S, Maleki S, Eriksson MJ, Caidahl K, Hamsten A, et al. Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study. Mol Med. 2011;17(11–12):1365–73.CrossRefPubMedPubMedCentral Folkersen L, Wagsater D, Paloschi V, Jackson V, Petrini J, Kurtovic S, Maleki S, Eriksson MJ, Caidahl K, Hamsten A, et al. Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study. Mol Med. 2011;17(11–12):1365–73.CrossRefPubMedPubMedCentral
5.
go back to reference Perrucci GL, Rurali E, Gowran A, Pini A, Antona C, Chiesa R, Pompilio G, Nigro P. Vascular smooth muscle cells in Marfan syndrome aneurysm: the broken bricks in the aortic wall. Cell Mol Life Sci. 2017;74(2):267–77.CrossRefPubMed Perrucci GL, Rurali E, Gowran A, Pini A, Antona C, Chiesa R, Pompilio G, Nigro P. Vascular smooth muscle cells in Marfan syndrome aneurysm: the broken bricks in the aortic wall. Cell Mol Life Sci. 2017;74(2):267–77.CrossRefPubMed
6.
go back to reference Li Y, Ren P, Dawson A, Vasquez HG, Ageedi W, Zhang C, Luo W, Chen R, Li Y, Kim S, et al. Single-cell transcriptome analysis reveals dynamic cell populations and Differential Gene expression patterns in control and Aneurysmal Human aortic tissue. Circulation. 2020;142(14):1374–88.CrossRefPubMedPubMedCentral Li Y, Ren P, Dawson A, Vasquez HG, Ageedi W, Zhang C, Luo W, Chen R, Li Y, Kim S, et al. Single-cell transcriptome analysis reveals dynamic cell populations and Differential Gene expression patterns in control and Aneurysmal Human aortic tissue. Circulation. 2020;142(14):1374–88.CrossRefPubMedPubMedCentral
7.
go back to reference Fan X, Peng J, Lei L, He J, Huang J, Zheng D, Xu W, Cai S, Chen J. Integrated analysis of immunocyte infiltration and differential gene expression in tricuspid aortic valve-associated thoracic aortic aneurysms. Ann Transl Med. 2020;8(6):285.CrossRefPubMedPubMedCentral Fan X, Peng J, Lei L, He J, Huang J, Zheng D, Xu W, Cai S, Chen J. Integrated analysis of immunocyte infiltration and differential gene expression in tricuspid aortic valve-associated thoracic aortic aneurysms. Ann Transl Med. 2020;8(6):285.CrossRefPubMedPubMedCentral
8.
go back to reference Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27(8):1133–63.CrossRefPubMed Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27(8):1133–63.CrossRefPubMed
9.
go back to reference Roychowdhury T, Lu H, Hornsby WE, Crone B, Wang GT, Guo DC, Sendamarai AK, Devineni P, Lin M, Zhou W, et al. Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm. Am J Hum Genet. 2021;108(9):1578–89.CrossRefPubMedPubMedCentral Roychowdhury T, Lu H, Hornsby WE, Crone B, Wang GT, Guo DC, Sendamarai AK, Devineni P, Lin M, Zhou W, et al. Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm. Am J Hum Genet. 2021;108(9):1578–89.CrossRefPubMedPubMedCentral
10.
go back to reference Orru V, Steri M, Sidore C, Marongiu M, Serra V, Olla S, Sole G, Lai S, Dei M, Mulas A, et al. Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat Genet. 2020;52(10):1036–45.CrossRefPubMedPubMedCentral Orru V, Steri M, Sidore C, Marongiu M, Serra V, Olla S, Sole G, Lai S, Dei M, Mulas A, et al. Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat Genet. 2020;52(10):1036–45.CrossRefPubMedPubMedCentral
11.
go back to reference Yu XH, Yang YQ, Cao RR, Bo L, Lei SF. The causal role of gut microbiota in development of osteoarthritis. Osteoarthritis Cartilage. 2021;29(12):1741–50.CrossRefPubMed Yu XH, Yang YQ, Cao RR, Bo L, Lei SF. The causal role of gut microbiota in development of osteoarthritis. Osteoarthritis Cartilage. 2021;29(12):1741–50.CrossRefPubMed
12.
go back to reference Genomes Project C, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74.CrossRef Genomes Project C, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74.CrossRef
13.
go back to reference Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for mendelian randomization. Stat Methods Med Res. 2017;26(5):2333–55.CrossRefPubMed Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for mendelian randomization. Stat Methods Med Res. 2017;26(5):2333–55.CrossRefPubMed
14.
go back to reference Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25.CrossRefPubMedPubMedCentral Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25.CrossRefPubMedPubMedCentral
15.
go back to reference Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in mendelian randomization with some Invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304–14.CrossRefPubMedPubMedCentral Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in mendelian randomization with some Invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304–14.CrossRefPubMedPubMedCentral
16.
go back to reference Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46(6):1985–98.CrossRefPubMedPubMedCentral Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46(6):1985–98.CrossRefPubMedPubMedCentral
17.
go back to reference Zhu G, Zhou S, Xu Y, Gao R, Li H, Zhai B, Liu X, He Y, Wang X, Han G, et al. Mendelian randomization study on the causal effects of omega-3 fatty acids on rheumatoid arthritis. Clin Rheumatol. 2022;41(5):1305–12.CrossRefPubMed Zhu G, Zhou S, Xu Y, Gao R, Li H, Zhai B, Liu X, He Y, Wang X, Han G, et al. Mendelian randomization study on the causal effects of omega-3 fatty acids on rheumatoid arthritis. Clin Rheumatol. 2022;41(5):1305–12.CrossRefPubMed
18.
go back to reference Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693–8.CrossRefPubMedPubMedCentral Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693–8.CrossRefPubMedPubMedCentral
19.
go back to reference Kucuksezer UC, Aktas Cetin E, Esen F, Tahrali I, Akdeniz N, Gelmez MY, Deniz G. The role of natural killer cells in Autoimmune diseases. Front Immunol. 2021;12:622306.CrossRefPubMedPubMedCentral Kucuksezer UC, Aktas Cetin E, Esen F, Tahrali I, Akdeniz N, Gelmez MY, Deniz G. The role of natural killer cells in Autoimmune diseases. Front Immunol. 2021;12:622306.CrossRefPubMedPubMedCentral
20.
go back to reference Tian Z, Zhang P, Li X, Jiang D. Analysis of immunogenic cell death in ascending thoracic aortic aneurysms based on single-cell sequencing data. Front Immunol. 2023;14:1087978.CrossRefPubMedPubMedCentral Tian Z, Zhang P, Li X, Jiang D. Analysis of immunogenic cell death in ascending thoracic aortic aneurysms based on single-cell sequencing data. Front Immunol. 2023;14:1087978.CrossRefPubMedPubMedCentral
21.
go back to reference Vorobjeva NV, Chelombitko MA, Sud’ina GF, Zinovkin RA, Chernyak BV. Role of Mitochondria in the Regulation of Effector Functions of Granulocytes. Cells 2023, 12(18). Vorobjeva NV, Chelombitko MA, Sud’ina GF, Zinovkin RA, Chernyak BV. Role of Mitochondria in the Regulation of Effector Functions of Granulocytes. Cells 2023, 12(18).
22.
go back to reference Wu D, Choi JC, Sameri A, Minard CG, Coselli JS, Shen YH, LeMaire SA. Inflammatory cell infiltrates in Acute and chronic thoracic aortic dissection. Aorta (Stamford). 2013;1(6):259–67.CrossRefPubMed Wu D, Choi JC, Sameri A, Minard CG, Coselli JS, Shen YH, LeMaire SA. Inflammatory cell infiltrates in Acute and chronic thoracic aortic dissection. Aorta (Stamford). 2013;1(6):259–67.CrossRefPubMed
23.
24.
go back to reference Ohkura N, Sakaguchi S. Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases. Cell Res. 2020;30(6):465–74.CrossRefPubMedPubMedCentral Ohkura N, Sakaguchi S. Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases. Cell Res. 2020;30(6):465–74.CrossRefPubMedPubMedCentral
25.
go back to reference Herrath J, Chemin K, Albrecht I, Catrina AI, Malmstrom V. Surface expression of CD39 identifies an enriched Treg-cell subset in the rheumatic joint, which does not suppress IL-17A secretion. Eur J Immunol. 2014;44(10):2979–89.CrossRefPubMed Herrath J, Chemin K, Albrecht I, Catrina AI, Malmstrom V. Surface expression of CD39 identifies an enriched Treg-cell subset in the rheumatic joint, which does not suppress IL-17A secretion. Eur J Immunol. 2014;44(10):2979–89.CrossRefPubMed
26.
go back to reference Ait-Oufella H, Wang Y, Herbin O, Bourcier S, Potteaux S, Joffre J, Loyer X, Ponnuswamy P, Esposito B, Dalloz M, et al. Natural regulatory T cells limit angiotensin II-induced aneurysm formation and rupture in mice. Arterioscler Thromb Vasc Biol. 2013;33(10):2374–9.CrossRefPubMed Ait-Oufella H, Wang Y, Herbin O, Bourcier S, Potteaux S, Joffre J, Loyer X, Ponnuswamy P, Esposito B, Dalloz M, et al. Natural regulatory T cells limit angiotensin II-induced aneurysm formation and rupture in mice. Arterioscler Thromb Vasc Biol. 2013;33(10):2374–9.CrossRefPubMed
27.
go back to reference Meher AK, Johnston WF, Lu G, Pope NH, Bhamidipati CM, Harmon DB, Su G, Zhao Y, McNamara CA, Upchurch GR Jr, et al. B2 cells suppress experimental abdominal aortic aneurysms. Am J Pathol. 2014;184(11):3130–41. Meher AK, Johnston WF, Lu G, Pope NH, Bhamidipati CM, Harmon DB, Su G, Zhao Y, McNamara CA, Upchurch GR Jr, et al. B2 cells suppress experimental abdominal aortic aneurysms. Am J Pathol. 2014;184(11):3130–41.
28.
go back to reference Kehagias D, Mulita F, Marlafeka I, Verras GI, Panagiotopoulos I, Kehagias I. Primary aortoenteric fistula: a rare complication of an eroding duodenal stent. Kardiochir Torakochirurgia Pol. 2022;19(3):161–3.PubMedPubMedCentral Kehagias D, Mulita F, Marlafeka I, Verras GI, Panagiotopoulos I, Kehagias I. Primary aortoenteric fistula: a rare complication of an eroding duodenal stent. Kardiochir Torakochirurgia Pol. 2022;19(3):161–3.PubMedPubMedCentral
29.
go back to reference Kehagias D, Mulita F, Panagiotopoulos I, Lampropoulos C, Markopoulos G, Verras GI, Kehagias I. Primary aortoenteric fistula: is endovascular repair the prime option? A review of the literature. Kardiochir Torakochirurgia Pol. 2022;19(4):220–5.PubMedPubMedCentral Kehagias D, Mulita F, Panagiotopoulos I, Lampropoulos C, Markopoulos G, Verras GI, Kehagias I. Primary aortoenteric fistula: is endovascular repair the prime option? A review of the literature. Kardiochir Torakochirurgia Pol. 2022;19(4):220–5.PubMedPubMedCentral
Metadata
Title
The causal relationship between thoracic aortic aneurysm and immune cells: a mendelian randomization study
Authors
Guoli Liu
Sha Pan
Hongli Xia
Mincai Li
Ansen Wu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2024
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-024-03876-1

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