Inflammatory cell infiltrates, hypoxia, vascularization, pentraxin 3 and osteoprotegerin in abdominal aortic aneurysms – A quantitative histological study
Autoři:
Tereza Blassova aff001; Zbynek Tonar aff001; Petr Tomasek aff001; Petr Hosek aff001; Ivana Hollan aff002; Vladislav Treska aff004; Jiri Molacek aff004
Působiště autorů:
Department of Histology and Embryology and Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
aff001; Hospital for Rheumatic Diseases, Lillehammer, Norway
aff002; Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America
aff003; Department of Vascular Surgery, University Hospital in Pilsen, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
aff004
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0224818
Souhrn
Information about the tissue characteristics of abdominal aortic aneurysms (AAAs), some of which may be reflected in the serum, can help to elucidate AAA pathogenesis and identify new AAA biomarkers. This information would be beneficial not only for diagnostics and follow-up but also for potential therapeutic intervention. Therefore, the aim of our study was to compare the expression of structural proteins, immune factors (T and B lymphocytes, macrophages, neutrophils and pentraxin 3 (PTX3)), osteoprotegerin (OPG), microvessels and hypoxic cells in AAA and nonaneurysmal aortic walls. We examined specimens collected during surgery for AAA repair (n = 39) and from the abdominal aortas of kidney donors without AAA (n = 8). Using histochemical and immunohistochemical methods, we quantified the areas positive for smooth muscle actin, desmin, elastin, collagen, OPG, CD3, CD20, MAC387, myeloperoxidase, PTX3, and hypoxia-inducible factor 1-alpha and the density of CD31-positive microvessels. AAA samples contained significantly less actin, desmin, elastin and OPG, more collagen, macrophages, neutrophils, T lymphocytes, B lymphocytes, hypoxic cells and PTX3, and a greater density of vasa vasorum (VV) than those in non-AAA samples. Hypoxia positively correlated with actin and negatively correlated with collagen. Microvascular density was related to inflammatory cell infiltrates, hypoxia, PTX3 expression and AAA diameter. The lower OPG expression in AAAs supports the notion of its protective role in AAA remodeling. AAA contained altered amounts of structural proteins, implying reduced vascular elasticity. PTX3 was upregulated in AAA and colocalized with inflammatory infiltrates. This evidence supports further evaluation of PTX3 as a candidate marker of AAA. The presence of aortic hypoxia, despite hypervascularization, suggests that hypoxia-induced neoangiogenesis may play a role in AAA pathogenesis. VV angiogenesis of the AAA wall increases its vulnerability.
Klíčová slova:
B cells – Histology – Hypoxia – Immunohistochemistry techniques – Inflammation – Macrophages – Medical hypoxia – Neutrophils
Zdroje
1. Kühnl A, Erk A, Trenner M, Salvermoser M, Schmid V, Eckstein H-H. Incidence, Treatment and Mortality in Patients with Abdominal Aortic Aneurysms: An Analysis of Hospital Discharge Data from 2005–2014. Dtsch Aerzteblatt Online. 2017; doi: 10.3238/arztebl.2017.0391 28655374
2. Eberlová L, Tonar Z, Witter K, Křížková V, Nedorost L, Korabečná M, et al. Asymptomatic Abdominal Aortic Aneurysms Show Histological Signs of Progression: a Quantitative Histochemical Analysis. Pathobiol J Immunopathol Mol Cell Biol. 2013;80: 11–23. doi: 10.1159/000339304 22797551
3. Billaud M, Hill JC, Richards TD, Gleason TG, Phillippi JA. Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic Aneurysm. Front Cardiovasc Med. 2018;5. doi: 10.3389/fcvm.2018.00124 30276199
4. Rodella LF, Rezzani R, Bonomini F, Peroni M, Cocchi MA, Hirtler L, et al. Abdominal Aortic Aneurysm and Histological, Clinical, Radiological Correlation. Acta Histochem. 2016;118: 256–262. doi: 10.1016/j.acthis.2016.01.007 26858185
5. Tanaka H, Zaima N, Sasaki T, Sano M, Yamamoto N, Saito T, et al. Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm. PloS One. 2015;10: e0134386. doi: 10.1371/journal.pone.0134386 26308526
6. 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. Pathobiol J Immunopathol Mol Cell Biol. 2009;76: 243–252. doi: 10.1159/000228900 19816084
7. Cieślik P, Hrycek A. Long Pentraxin 3 (PTX3) in the Light of Its Structure, Mechanism of Action and Clinical Implications. Autoimmunity. 2012;45: 119–128. doi: 10.3109/08916934.2011.611549 21988562
8. Bonacina F, Baragetti A, Catapano AL, Norata GD. Long Pentraxin 3: Experimental and Clinical Relevance in Cardiovascular Diseases. Mediators Inflamm. 2013;2013: 1–10. doi: 10.1155/2013/725102 23690668
9. Yigit S, Sari S, Canbolat IP, Arat Ozkan A, Ersanli MK, Gurmen T. Pentraxin-3 a Novel Biomarker for Predicting Coronary Artery Disease. Eur Heart J. 2013;34: P3108–P3108. doi: 10.1093/eurheartj/eht309.P3108
10. Buda V, Andor M, Tomescu MC, Cristescu C, Voicu M, Citu I, et al. P2637ACE Inhibitors and ARBs Decrease More Powerful the PTX-3 Plasma Levels of Hypertensive Patients with Endothelial Dysfunction Compared with Other Anti-Hypertensive Drugs, in a Chronic Treatment. Eur Heart J. 2017;38. doi: 10.1093/eurheartj/ehx502.P2637
11. Nakamura A, Miura S, Shiga Y, Norimatsu K, Miyase Y, Suematsu Y, et al. Is Pentraxin 3 a Biomarker, a Player, or Both in the Context of Coronary Atherosclerosis and Metabolic Factors? Heart Vessels. 2015;30: 752–761. doi: 10.1007/s00380-014-0553-0 25048680
12. Norata GD, Garlanda C, Catapano AL. The Long Pentraxin PTX3: A Modulator of the Immunoinflammatory Response in Atherosclerosis and Cardiovascular Diseases. Trends Cardiovasc Med. 2010;20: 35–40. doi: 10.1016/j.tcm.2010.03.005 20656213
13. Koole D, Hurks R, Schoneveld A, Vink A, Golledge J, Moran CS, et al. Osteoprotegerin Is Associated with Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease. Arterioscler Thromb Vasc Biol. 2012;32: 1497–1504. doi: 10.1161/ATVBAHA.111.243592 22516062
14. Callegari A, Coons ML, Ricks JL, Rosenfeld ME, Scatena M. Increased Calcification in Osteoprotegerin-Deficient Smooth Muscle Cells: Dependence on Receptor Activator of NF-κB Ligand and Interleukin 6. J Vasc Res. 2014;51: 118–131. doi: 10.1159/000358920 24642764
15. Morony S, Tintut Y, Zhang Z, Cattley RC, Van G, Dwyer D, et al. Osteoprotegerin Inhibits Vascular Calcification without Affecting Atherosclerosis in Ldlr(-/-) Mice. Circulation. 2008;117: 411–420. doi: 10.1161/CIRCULATIONAHA.107.707380 18172035
16. Jono S, Ikari Y, Shioi A, Mori K, Miki T, Hara K, et al. Serum Osteoprotegerin Levels Are Associated with the Presence and Severity of Coronary Artery Disease. Circulation. 2002;106: 1192–1194. doi: 10.1161/01.cir.0000031524.49139.29 12208791
17. Moran CS, McCann M, Karan M, Norman P, Ketheesan N, Golledge J. Association of Osteoprotegerin With Human Abdominal Aortic Aneurysm Progression. Circulation. 2005;111: 3119–3125. doi: 10.1161/CIRCULATIONAHA.104.464727 15939823
18. Bennett BJ, Scatena M, Kirk EA, Rattazzi M, Varon RM, Averill M, et al. Osteoprotegerin Inactivation Accelerates Advanced Atherosclerotic Lesion Progression and Calcification in Older ApoE-/- Mice. Arterioscler Thromb Vasc Biol. 2006;26: 2117–2124. doi: 10.1161/01.ATV.0000236428.91125.e6 16840715
19. Bumdelger B, Kokubo H, Kamata R, Fujii M, Yoshimura K, Aoki H, et al. Osteoprotegerin Prevents Development of Abdominal Aortic Aneurysms. PloS One. 2016;11: e0147088. doi: 10.1371/journal.pone.0147088 26783750
20. Bancroft JD, Gamble M. Theory and Practice of Histological Techniques. [Edinburgh]: Churchill Livingstone; 2008.
21. Kocová J. Overall Staining of Connective Tissue and the Muscular Layer of Vessels. Folia Morphol. 1970;18: 293–295.
22. Rich L, Whittaker P. Collagen and Picrosirius Red Staining: a Polarized Light Assessment of Fibrillar Hue and Spatial Distribution. Braz J Morphol Sci. 2005;2005: 97–104.
23. Kubíková T, Kochová P, Brázdil J, Špatenka J, Burkert J, Králíčková M, et al. The Composition and Biomechanical Properties of Human Cryopreserved Aortas, Pulmonary Trunks, and Aortic and Pulmonary Cusps. Ann Anat—Anat Anz. 2017;212: 17–26. doi: 10.1016/j.aanat.2017.03.004 28434910
24. Tonar Z, Tomášek P, Loskot P, Janáček J, Králíčková M, Witter K. Vasa Vasorum in the Tunica Media and Tunica Adventitia of the Porcine Aorta. Ann Anat—Anat Anz. 2016;205: 22–36. doi: 10.1016/j.aanat.2016.01.008 26844625
25. Houdek K, Moláček J, Třeška V, Křížková V, Eberlová L, Boudová L, et al. Focal Histopathological Progression of Porcine Experimental Abdominal Aortic Aneurysm is Mitigated by Atorvastatin. Int Angiol J Int Union Angiol. 2013;32: 291–306.
26. Mouton PR. Principles and Practices of Unbiased Stereology: an Introduction for Bioscientists. Baltimore: Johns Hopkins University Press; 2002.
27. Tonar Z, Kubíková T, Prior C, Demjén E, Liška V, Králíčková M, et al. Segmental and Age Differences in the Elastin Network, Collagen, and Smooth Muscle Phenotype in the Tunica Media of the Porcine Aorta. Ann Anat Anat Anz Off Organ Anat Ges. 2015;201: 79–90. doi: 10.1016/j.aanat.2015.05.005 26232584
28. Tonar Z, Egger GF, Witter K, Wolfesberger B. Quantification of Microvessels in Canine Lymph Nodes. Microsc Res Tech. 2008;71: 760–772. doi: 10.1002/jemt.20619 18615685
29. Howard V, Reed MG. Unbiased Stereology: Three-Dimensional Measurement in Microscopy. Liverpool: QTP; 2010.
30. Witter K, Tonar Z, Schöpper H. How many Layers has the Adventitia?—Structure of the Arterial Tunica Externa Revisited. Anat Histol Embryol. 2017;46: 110–120. doi: 10.1111/ahe.12239 27282337
31. Holmes DR, Liao S, Parks WC, Thompson RW. Medial Neovascularization in Abdominal aortic Aneurysms: a Histopathologic Marker of Aneurysmal Degeneration with Pathophysiologic Implications. J Vasc Surg. 1995;21: 761–771; discussion 771–772. doi: 10.1016/s0741-5214(05)80007-2 7539511
32. Tanaka H, Unno N, Yata T, Kugo H, Zaima N, Sasaki T, et al. Creation of a Rodent Model of Abdominal Aortic Aneurysm by Blocking Adventitial Vasa Vasorum Perfusion. J Vis Exp. 2017; doi: 10.3791/55763 29155740
33. Vorp DA, Lee PC, Wang DH, Makaroun MS, Nemoto EM, Ogawa S, et al. Association of Intraluminal Thrombus in Abdominal Aortic Aneurysm with Local Hypoxia and Wall Weakening. J Vasc Surg. 2001;34: 291–299. doi: 10.1067/mva.2001.114813 11496282
34. Tanaka H, Zaima N, Sasaki T, Hayasaka T, Goto-Inoue N, Onoue K, et al. Adventitial Vasa Vasorum Arteriosclerosis in Abdominal Aortic Aneurysm. PloS One. 2013;8: e57398. doi: 10.1371/journal.pone.0057398 23460850
35. Popescu MR, Butcovan D, Folescu R, Motoc A, Zamfir CL. Thoracic Aorta Dissection—Assessment of Aortic Adventitia Involvement. Rom J Leg Med. 2013;21: 207–2014. doi: 0.4323/rjlm.2013.207
36. Gäbel G, Northoff BH, Weinzierl I, Ludwig S, Hinterseher I, Wilfert W, et al. Molecular Fingerprint for Terminal Abdominal Aortic Aneurysm Disease. J Am Heart Assoc. 2017;6. doi: 10.1161/JAHA.117.006798 29191809
37. Tsai S-H, Huang P-H, Hsu Y-J, Peng Y-J, Lee C-H, Wang J-C, et al. Inhibition of Hypoxia Inducible Factor-1α Attenuates Abdominal Aortic Aneurysm Progression through the Down-Regulation of Matrix Metalloproteinases. Sci Rep. 2016;6: 28612. doi: 10.1038/srep28612 27363580
38. Docherty CK, Nilsen M, MacLean MR. Influence of 2-Methoxyestradiol and Sex on Hypoxia-Induced Pulmonary Hypertension and Hypoxia-Inducible Factor-1-α. J Am Heart Assoc. 2019;8: e011628. doi: 10.1161/JAHA.118.011628 30819028
39. Sawada H, Naito Y, Oboshi M, Iwasaku T, Morisawa D, Okuhara Y, et al. Pentraxin 3 Expression in Human Abdominal Aortic Aneurysm. Circulation. 2014;2014: A15060.
40. Sawada H, Naito Y, Oboshi M, Soyama Y, Nishimura K, Eguchi A, et al. Increment of Pentraxin3 Expression in Abdominal Aortic Aneurysm. Int J Cardiol. 2015;195: 281–282. doi: 10.1016/j.ijcard.2015.05.177 26056957
41. Molacek J, Treska V, Zeithaml J, Hollan I, Topolcan O, Pecen L, et al. Blood Biomarker Panel Recommended for Personalized Prediction, Prognosis, and Prevention of Complications Associated with Abdominal Aortic Aneurysm. EPMA J. 2019;10: 125–135. doi: 10.1007/s13167-019-00173-2 31258818
42. Arao K, Fujiwara T, Taniguchi Y, Jinnouchi H, Sasai H, Matsumoto M, et al. Implications of Pentraxin 3 Levels in Patients with Acute Aortic Dissection. Heart Vessels. 2015;30: 211–217. doi: 10.1007/s00380-014-0470-2 24474442
43. Folsom Aaron R., Yao Lu, Alonso Alvaro, Lutsey Pamela L., Missov Emil, Lederle Frank A., et al. Circulating Biomarkers and Abdominal Aortic Aneurysm Incidence. Circulation. 2015;132: 578–585. doi: 10.1161/CIRCULATIONAHA.115.016537 26085454
44. Henriksson AE, Lindqvist M, Sihlbom C, Bergström J, Bylund D. Identification of Potential Plasma Biomarkers for Abdominal Aortic Aneurysm Using Tandem Mass Tag Quantitative Proteomics. Proteomes. 2018;6. doi: 10.3390/proteomes6040043 30340394
45. Moris D, Mantonakis E, Avgerinos E, Makris M, Bakoyiannis C, Pikoulis E, et al. Novel Biomarkers of Abdominal Aortic Aneurysm Disease: Identifying Gaps and Dispelling Misperceptions. BioMed Res Int. 2014;2014: 1–13. doi: 10.1155/2014/925840 24967416
46. Urbonavicius S, Urbonaviciene G, Honoré B, Henneberg EW, Vorum H, Lindholt JS. Potential Circulating Biomarkers for Abdominal Aortic Aneurysm Expansion and Rupture—a Systematic Review. Eur J Vasc Endovasc Surg. 2008;36: 273–280. doi: 10.1016/j.ejvs.2008.05.009 18639476
47. Fornai F, Carrizzo A, Forte M, Ambrosio M, Damato A, Ferrucci M, et al. The Inflammatory Protein Pentraxin 3 in Cardiovascular Disease. Immun Ageing A. 2016;13: 25. doi: 10.1186/s12979-016-0080-1 27559355
48. Cabiati M, Svezia B, Verde A, Caselli C, Del Ry S. P3401Pentraxin 3, a Novel Inflammatory Marker in Heart Failure Patients: Its Expression in Circulating Leukocytes as a Function of Clinical Severity. Eur Heart J. 2017;38. doi: 10.1093/eurheartj/ehx504.P3401
49. Liu H, Guan S, Fang W, Yuan F, Zhang M, Qu X. Associations Between Pentraxin 3 and Severity of Coronary Artery Disease. BMJ Open. 2015;5: e007123. doi: 10.1136/bmjopen-2014-007123 25854969
50. Kinoshita M, Yokote K, Arai H, Iida M, Ishigaki Y, Ishibashi S, et al. Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2017. J Atheroscler Thromb. 2018;25: 846–984. doi: 10.5551/jat.GL2017 30135334
51. Armstrong PJ, Johanning JM, Calton WC, Delatore JR, Franklin DP, Han DC, et al. Differential Gene Expression in Human Abdominal Aorta: Aneurysmal versus Occlusive Disease. J Vasc Surg. 2002;35: 346–14. doi: 10.1067/mva.2002.121071 11854734
52. Patel R, Sweeting MJ, Powell JT, Greenhalgh RM. Endovascular Versus Open Repair of Abdominal Aortic Aneurysm in 15-years’ Follow-up of the UK Endovascular Aneurysm Repair Trial 1 (EVAR Trial 1): a Randomised Controlled Trial. The Lancet. 2016;388: 2366–2374. doi: 10.1016/S0140-6736(16)31135-7
Článek vyšel v časopise
PLOS One
2019 Číslo 11
- S diagnostikou Parkinsonovy nemoci může nově pomoci AI nástroj pro hodnocení mrkacího reflexu
- Proč při poslechu některé muziky prostě musíme tančit?
- Je libo čepici místo mozkového implantátu?
- Chůze do schodů pomáhá prodloužit život a vyhnout se srdečním chorobám
- Pomůže v budoucnu s triáží na pohotovostech umělá inteligence?
Nejčtenější v tomto čísle
- A daily diary study on maladaptive daydreaming, mind wandering, and sleep disturbances: Examining within-person and between-persons relations
- A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction
- A substitution mutation in a conserved domain of mammalian acetate-dependent acetyl CoA synthetase 2 results in destabilized protein and impaired HIF-2 signaling
- Molecular validation of clinical Pantoea isolates identified by MALDI-TOF
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy