Pathogenesis of abdominal aortic aneurysm – the role of inflammation and proteolysis

Aldona Siennicka, Monika Adamowicz, Natalie Grzesch

Abstract


Clinical studies show that the morbidity rate for abdominal aortic aneurysms (AAAs) is high, especially among older people. A lack of early diagnosis carries a high risk of fatality. Abdominal
aortic aneurysm formation is connected to, among others, inflammatory mediators, proteolytic degradation of the extracellular matrix and genetic predispositions. Additionally, a crucial
part of this process is played by the presence of intraluminal thrombus, which participates in the inflammatory reactions and proteolysis contributing to the degradation of the wall’s building
elements. Intraluminal thrombus and inflammatory cells’ which infiltrate the vessel wall characterize the pathogenesis of AAA. The dominant population of cells is lymphocytes T and B, neutrophils, monocytes/macrophages, natural killer (NK) cells, as well as mast cells, which produce different inflammatory factors and mediators which contribute to collagen, elastin and smooth muscle cell degradation in the aortic wall. The intensified inflammatory process may lead to increased proteolytic enzyme activity that is necessary for the progression and rupture of the aneurysm. In the presented paper, we show the participation of inflammatory factors in the pathogenesis of AAA and review chosen mediators of inflammation and proteolysis. A better understanding of the immunological mechanisms in the pathogenesis of AAA may help in modulation, innovation, and improvements in methods of treatment.


Keywords


abdominal aortic aneurysm; inflammation; cytokine; interleukin-1β; interleukin-6; metalloproteinases; neutrophil gelatinase-associated lipocalin

Full Text:

PDF

References


Kumar Y, Hooda K, Li S, Goyal P, Gupta N, Adeb M. Abdominal aortic aneurysm: pictorial review of common appearances and complications. Ann Transl Med 2017;5(12):256.

Wanhainen A, Verzini F, Van Herzeele I, Allaire E, Bown M, Cohnert T, et al. Editor’s Choice – European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms. Eur J Vasc Endovasc Surg 2019;57(1):8-93.

Mussa FF. Screening for abdominal aortic aneurysm. J Vasc Surg 2015;62(3):774-8.

Michel JB, Martin-Ventura JL, Egido J, Sakalihasan N, Treska V, Lindholt J, et al. Novel aspects of the pathogenesis of aneurysms of the abdominal aorta in humans. Cardiovasc Res 2011;90(1):18-27.

Bhagavan D, Di Achille P, Humphrey JD. Strongly coupled morphological features of aortic aneurysms drive intraluminal thrombus. Sci Rep 2018;8(1):13273.

Piechota-Polanczyk A, Jozkowicz A, Nowak W, Eilenberg W, Neumayer C, Malinski T, et al. The abdominal aortic aneurysm and intraluminal thrombus: current concepts of development and treatment. Front Cardiovasc Med 2015;2:19.

Ullery BW, Hallett RL, Fleischmann D. Epidemiology and contemporary management of abdominal aortic aneurysms. Abdom Radiol 2018;43(5):1032-43.

Kim HO, Yim NY, Kim JK, Kang YJ, Lee BC. Endovascular aneurysm repair for abdominal aortic aneurysm: a comprehensive review. Korean J Radiol 2019;20(8):1247-65.

Komutrattananont P, Mahakkanukrauh P, Das S. Morphology of the human aorta and age-related changes: anatomical facts. Anat Cell Biol 2019;52(2):109-14.

Kuivaniemi H, Ryer EJ, Elmore JR, Tromp G. Understanding the pathogenesis of abdominal aortic aneurysms. Expert Rev Cardiovasc Ther 2015;13(9):975-87.

Leung J, Wright A, Cheshire N, Thom SA, Hughes AD, Xu XY. Flow patterns and wall shear stresses in patient-specific models of the abdominal aortic aneurysm. Stud Health Technol Inform 2004;103:235-42.

Tamura T, Jamous MA, Kitazato KT, Yagi K, Tada Y, Uno M, et al. Endothelial damage due to impaired nitric oxide bioavailability triggers cerebral aneurysm formation in female rats. J Hypertens 2009;27(6):1284-92.

Martinez-Pinna R, Madrigal-Matute J, Tarin C, Burillo E, Esteban-Salan M, Pastor-Vargas C, et al. Proteomic analysis of intraluminal thrombus highlights complement activation in human abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 2013;33(8):2013-20.

Shimizu K, Mitchell RN, Libby P. Inflammation and cellular immune responses in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 2006;26(5):987-94.

Anzai T. Inflammatory Mechanisms of Cardiovascular Remodeling. Circ J 2018;82(3):629-35.

Adolph R, Vorp DA, Steed DL, Webster MW, Kameneva MV, Watkins SC. Cellular content and permeability of intraluminal thrombus in abdominal aortic aneurysm. J Vasc Surg 1997;25(5):916-26.

Eliason JL, Hannawa KK, Ailawadi G, Sinha I, Ford JW, Deogracias MP, et al. Neutrophil depletion inhibits experimental abdominal aortic aneurysm formation. Circulation 2005;112(2):232-40.

Kadoglou NP, Liapis CD. Matrix metalloproteinases: contribution to pathogenesis, diagnosis, surveillance and treatment of abdominal aortic aneurysms. Curr Med Res Opin 2004;20(4):419-32.

Samadzadeh KM, Chun KC, Nguyen AT, Baker PM, Bains S, Lee ES. Monocyte activity is linked with abdominal aortic aneurysm diameter. J Surg Res 2014;190(1):328-34.

Cione E, Piegari E, Gallelli G, Caroleo MC, Lamirata E, Curcio F, et al. Expression of MMP-2, MMP-9, and NGAL in tissue and serum of patients with vascular aneurysms and their modulation by statin treatment: a pilot study. Biomolecules 2020;10(3):359.

Reeps C, Pelisek J, Seidl S, Schuster T, Zimmermann A, Kuehnl A, et al. Inflammatory infiltrates and neovessels are relevant sources of MMPs in abdominal aortic aneurysm wall. Pathobiology 2009;76(5):243-52.

Łukasiewicz A, Reszec J, Kowalewski R, Chyczewski L, Łebkowska U. Assessment of inflamatory infiltration and angiogenesis in the thrombus and the wall of abdominal aortic aneurysms on the basis of histological parameters and computed tomography angiography study. Folia Histochem Cytobiol 2012;50(4):547-53.

Sawada H, Hao H, Naito Y, Oboshi M, Hirotani S, Mitsuno M, et al. Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic. Arterioscler Thromb Vasc Biol 2015;35(6):1507-14.

Delbosc S, Diallo D, Dejouvencel T, Lamiral Z, Louedec L, Martin-Ventura JL, et al. Impaired high-density lipoprotein anti-oxidant capacity in human abdominal aortic aneurysm. Cardiovasc Res 2013;100(2):307-15.

Tilson MD. Autoimmunity in the abdominal aortic aneurysm and its association with smoking. Aorta (Stamford) 2017;5(6):159-67.

Blanchard JF, Armenian HK, Peeling R, Friesen PP, Shen C, Brunham RC. The relation between Chlamydia pneumoniae infection and abdominal aortic aneurysm: case-control study. Clin Infect Dis 2000;30(6):946-7.

Ocana E, Bohórquez JC, Pérez-Requena J, Brieva JA, Rodríguez C. Characterisation of T and B lymphocytes infiltrating abdominal aortic aneurysms. Atherosclerosis 2003;170(1):39-48.

Joviliano EE, Ribeiro MS, Tenorio EJR. MicroRNAs and current concepts on the pathogenesis of abdominal aortic aneurysm. Braz J Cardiovasc Surg 2017;32(3):215-24.

Raphael I, Nalawade S, Eagar TN, Forsthuber TG. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 2015;74(1):5-17.

Fietta P, Delsante G. The effector T helper cell triade. Riv Biol 2009;102(1):61-74.

Xiong W, Zhao Y, Prall A, Greiner TC, Baxter BT. Key roles of CD4+ T cells and IFN-gamma in the development of abdominal aortic aneurysms in a murine model. J Immunol 2004;172(4):2607-12.

Schönbeck U, Sukhova GK, Gerdes N, Libby P. T(H)2 predominant immune responses prevail in human abdominal aortic aneurysm. Am J Pathol 2002;161(2):499-506.

Cassimjee I, Regent L, Jyoti P. Inflammatory mediators in abdominal aortic aneurysms. Aortic aneurysm. In: Kirali K, editor. Aortic Aneurysm. Intech Open; 2017. p. 79-90.

Raffort J, Lareyre F, Clément M, Hassen-Khodja R, Chinetti G, Mallat Z. Monocytes and macrophages in abdominal aortic aneurysm. Nat Rev Cardiol 2017;14(8):457-71.

Davies LC, Jenkins SJ, Allen JE, Taylor PR. Tissue-resident macrophages. Nat Immunol 2013;14(10):986-95.

Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014;41(1):14-20.

Vucevic D, Maravic-Stojkovic V, Vasilijic S, Borovic-Labudovic M, Majstorovic I, Radak D, et al. Inverse production of IL-6 and IL-10 by abdominal aortic aneurysm explant tissues in culture. Cardiovasc Pathol 2012;21(6):482-9.

Dale MA, Xiong W, Carson JS, Suh MK, Karpisek AD, Meisinger TM, et al. Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization. J Immunol 2016;196(11):4536-43.

Ghigliotti G, Barisione C, Garibaldi S, Brunelli C, Palmieri D, Spinella G, 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(2):131-42.

Kim HW, Blomkalns AL, Ogbi M, Thomas M, Gavrila D, Neltner BS, et al. Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine. Am J Physiol Heart Circ Physiol 2017;313(6):H1168-79.

Ramos-Mozo P, Madrigal-Matute J, Martinez-Pinna R, Blanco-Colio LM, Lopez JA, Camafeita E, et al. Proteomic analysis of polymorphonuclear neutrophils identiies catalase as a novel biomarker of abdominal aortic aneurysm: potential implication of oxidative stress in abdominal aortic aneurysm progression. Arterioscler Thromb Vasc Biol 2011;31(12):3011-9.

Ramos-Mozo P, Madrigal-Matute J, Vega de Ceniga M, Blanco-Colio LM, Meilhac O, Feldman L, et al. Increased plasma levels of NGAL, a marker of neutrophil activation, in patients with abdominal aortic aneurysm. Atherosclerosis 2012;220(2):552-6.

Teng N, Maghzal GJ, Talib J, Rashid I, Lau AK, Stocker R. The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture. Redox Rep 2017;22(2):51-73.

Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev 2011;22(4):189-95.

Peshkova IO, Schaefer G, Koltsova EK. Atherosclerosis and aortic aneurysm – is inflammation a common denominator? FEBS J 2016;283(9):1636-52.

Aria H, Kalani M, Hodjati H, Doroudchi M. Elevated levels of IL-6 and IL-9 in the sera of patients with AAA do not correspond to their production by peripheral blood mononuclear cells. Artery Res 2018;21(C):43-52.

Harrison SC, Smith AJP, Jones GT, Swerdlow DI, Rampuri R, Bown MJ, et al. Interleukin-6 receptor pathways in abdominal aortic aneurysm. Eur Heart J 2013;34(48):3707-16.

Kokje VBC, Gäbel G, Koole D, Northoff BH, Holdt LM, Hamming JF, et al. IL-6: a Janus-like factor in abdominal aortic aneurysm disease. Atherosclerosis 2016;251:139-46.

Lindberg S, Zarrouk M, Holst J, Gottsäter A. Inflammatory markers associated with abdominal aortic aneurysm. Eur Cytokine Netw 2016;27(3):75-80.

Wang Q, Ren J, Morgan S, Liu Z, Dou C, Liu B. Monocyte chemoattractant protein-1 (MCP-1) regulates macrophage cytotoxicity in abdominal aortic aneurysm. PloS One 2014;9(3):e92053.

Apostolakis S, Vogiatzi K, Amanatidou V, Spandidos DA. Interleukin 8 and cardiovascular disease. Cardiovasc Res 2009;84(3):353-60.

Karwowska A, Kurianiuk A, Łapiński R, Gacko M, Karczewski J. Epidemiology of abdominal aortic aneurysm. Prog Health Sci 2015;5(1):238-45.

Kokje VBC, Gäbel G, Dalman RL, Koole D, Northoff BH, Holdt LM, et al. CXCL8 hyper-signaling in the aortic abdominal aneurysm. Cytokine 2018;108:96-104.

Ohno T, Aoki H, Ohno S, Nishihara M, Furusho A, Hiromatsu S, et al. Cytokine profile of human abdominal aortic aneurysm: involvement of JAK/STAT pathway. Ann Vasc Dis 2018;11(1):84-90.

Sano M, Sasaki T, Hirakawa S, Sakabe J, Ogawa M, Baba S, et al. Lymphangiogenesis and Angiogenesis in Abdominal Aortic Aneurysm. PLoS One 2014;9(3):e89830.

Hamano K, Li TS, Takahashi M, Kobayashi T, Shirasawa B, Ito H, et al. Enhanced tumor necrosis factor-alpha expression in small sized abdominal aortic aneurysm. World J Surg 2003;27(4):476-80.

Xiong W, MacTaggart J, Knispel R, Worth J, Persidsky Y, Baxter BT. Blocking TNF-alpha attenuates aneurysm formation in a murine model. J Immunol 2009;183(4):2741-6.

Sheth RA, Maricevich M, Mahmood U. In vivo optical molecular imaging of matrix metalloproteinase activity in abdominal aortic aneurysms correlates with treatment effects on growth rate. Atherosclerosis 2010;212(1):181-7.

Sangiorgi G, D’Averio R, Mauriello A, Bondio M, Pontillo M, Castelvecchio S, et al. Plasma levels of metalloproteinases-3 and -9 as markers of successful abdominal aortic aneurysm exclusion after endovascular graft treatment. Circulation 2001;104:288-95.

Loria V, Dato I, Graziani F, Biasucci LM. Myeloperoxidase: a new biomarker of inflammation in ischemic heart disease and acute coronary syndromes. Mediators Inflamm 2008;2008:135625.

Serra R, Grande R, Montemurro R, Butrico L, Caliò FG, Mastrangelo D, et al. The role of matrix metalloproteinases and neutrophil gelatinase-associated lipocalin in central and peripheral arterial aneurysms. Surgery 2015;157(1):155-62.




DOI: https://doi.org/10.21164/pomjlifesci.766

Copyright (c) 2021 Aldona Siennicka, Monika Adamowicz, Natalie Grzesch

License URL: https://creativecommons.org/licenses/by-nc-nd/3.0/pl/