Covid-19 Research

Research Article

OCLC Number/Unique Identifier: 9041817786

Neutrophil to Lymphocyte Ratio Reflects the Proteolytic Activity of the Abdominal Aortic Aneurysm Wall

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Vasile Aurelian Sasarman, Octavian Andercou*, Schjoth Bruno, Manuel Chira, Alexandru Oprea, Catalin Trifan and Dan Bindea

Volume2-Issue5
Dates: Received: 2021-05-17 | Accepted: 2021-05-19 | Published: 2021-05-20
Pages: 339-342

Abstract

Background: This study aims to evaluate the local proteolytic activity from the level of Abdominal Aortic Aneurysm (AAA) wall and correlate the obtained values with the preoperative values of NLRs (Neutrophil-Lymphocyte Ratio), evaluating a possible association between the two variables and, implicitly, between the local proteolysis process and the systemic inflammatory response of those patients diagnosed with AAA.

Methods: The current study is monocentric, observational, and prospective, taking place at the Department of Cardiovascular Surgery, Cluj-Napoca, Romania. Patients undergoing elective or emergency classical surgery for unruptured AAA or ruptured AAA were included in the study. During classical surgery, samples from the infrarenal aortic aneurysmal wall were collected in a standardized manner, from the central part of the anterior wall from uAAA and rAAA and were analyzed by gel zymography.
Results: The concentration of MMP2 was similar in the ruptured/non-ruptured group, without any statistical significance. In the MMP-9 case, we obtained a mean of 821.35 U arb/µg at the level of unruptured aneurysmal wall and 1411.57 U arb/µg at the level of the ruptured aneurysmal wall. According to the ANOVA test, there is a significant difference between the two categories of aneurysms. The same correlation was observed regarding both the zymogen category, pro-MMP-2, as well as pro-MMP-9: they expressed significant higher quantities of inactive enzymes in rAAA.

We splitted the study population into two categories: patients who presented preoperative NLR values < 5 and > 5. MMP-2 collagenase levels did not register statistical differences between the two groups, p = 0.3236. High levels of MMP-9 are positively associated with increased values of NLR, the NLR<5 group had an MMP-9 mean of 902.41(473.71) U arb/µg, statistically lower than the MMP-9 mean indicated in the NLR>5 group, 1474(521.21) U arb/µg. Similarly, MMP-2 and MMP-9 zymogens were found in statistically higher quantities (p < 0.05) in the NLR>5 group of patients.

Conclusions: This is the first study that analyzes a possible correlation between the local proteolytic activity at the site of the dilated aneurysmal aortic wall and circulating levels of NLR. Following the results obtained, we conclude that the group of patients presenting with NLR>5 preoperatively, as in the rAAA group, significantly greater levels of MMP-9 and inactive proenzymes were identified. Local metalloproteinase MM9 activity is proportional to the systemic inflammatory activity. Concomitantly, we hypothesize that the increased sensitivity of NLR as a prognostic marker in AAA pathology, which is ensured and confirmed by its strong association with local proteolytic activity, directly implied in the evolution of the disease.

FullText HTML FullText PDF DOI: 10.37871/jbres1238


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Copyright

© 2021 Sasarman VA, et al. Distributed under Creative Commons CC-BY 4.0

How to cite this article

Sasarman VA, Andercou O, Bruno S, Chira M, Oprea A, Trifan C, Bindea D. Neutrophil to Lymphocyte Ratio Reflects the Proteolytic Activity of the Abdominal Aortic Aneurysm Wall. J Biomed Res Environ Sci. 2021 May 20; 2(5): 339-342. doi: 10.37871/jbres1238, Article ID: jbres1238


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References


  1. Kent KC. Clinical practice. Abdominal aortic aneurysms. N Engl J Med. 2014 Nov 27;371(22):2101-8. doi: 10.1056/NEJMcp1401430. PMID: 25427112.
  2. Maguire EM, Pearce SWA, Xiao R, Oo AY, Xiao Q. Matrix Metalloproteinase in Abdominal Aortic Aneurysm and Aortic Dissection. Pharmaceuticals (Basel). 2019 Aug 6;12(3):118. doi: 10.3390/ph12030118. PMID: 31390798; PMCID: PMC6789891.
  3. Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest. 2002 Sep;110(5):625-32. doi: 10.1172/JCI15334. PMID: 12208863; PMCID: PMC151106.
  4. Patel MI, Melrose J, Ghosh P, Appleberg M. Increased synthesis of matrix metalloproteinases by aortic smooth muscle cells is implicated in the etiopathogenesis of abdominal aortic aneurysms. J Vasc Surg. 1996 Jul;24(1):82-92. doi: 10.1016/s0741-5214(96)70148-9. PMID: 8691532.
  5. Sasaguri Y, Murahashi N, Sugama K, Kato S, Hiraoka K, Satoh T, Isomoto H, Morimatsu M. Development-related changes in matrix metalloproteinase expression in human aortic smooth muscle cells. Lab Invest. 1994 Aug;71(2):261-9. PMID: 8078305.
  6. Wilson WR, Anderton M, Schwalbe EC, Jones JL, Furness PN, Bell PR, Thompson MM. Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture. Circulation. 2006 Jan 24;113(3):438-45. doi: 10.1161/CIRCULATIONAHA.105.551572. PMID: 16432074.
  7. Bedeleanu D, Coman C, Encica S, Hagiu R, Molnar A, Cãpâlneanu R. Stanford type A aortic dissection in a hypertensive patient with atherosclerosis of aorta and aortitis. Echocardiography. 2000 Feb;17(2):181-5. doi: 10.1111/j.1540-8175.2000.tb01122.x. PMID: 10978979.
  8. Lipka D, Boratyński J. Metaloproteinazy MMP. Struktura i funkcja [Metalloproteinases. Structure and function]. Postepy Hig Med Dosw (Online). 2008 Jul 3;62:328-36. Polish. PMID: 18614970.
  9. Davis V, Persidskaia R, Baca-Regen L, Itoh Y, Nagase H, Persidsky Y, Ghorpade A, Baxter BT. Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1625-33. doi: 10.1161/01.atv.18.10.1625. PMID: 9763536.
  10. McMillan WD, Tamarina NA, Cipollone M, Johnson DA, Parker MA, Pearce WH. Size matters: the relationship between MMP-9 expression and aortic diameter. Circulation. 1997 Oct 7;96(7):2228-32. doi: 10.1161/01.cir.96.7.2228. PMID: 9337194.
  11. Petersen E, Gineitis A, WÃ¥gberg F, Angquist KA. Activity of matrix metalloproteinase-2 and -9 in abdominal aortic aneurysms. Relation to size and rupture. Eur J Vasc Endovasc Surg. 2000 Nov;20(5):457-61. doi: 10.1053/ejvs.2000.1211. PMID: 11112465.
  12. Manicone AM, McGuire JK. Matrix metalloproteinases as modulators of inflammation. Semin Cell Dev Biol. 2008 Feb;19(1):34-41. doi: 10.1016/j.semcdb.2007.07.003. Epub 2007 Jul 10. PMID: 17707664; PMCID: PMC2235912.
  13. Brophy CM, Reilly JM, Smith GJ, Tilson MD. The role of inflammation in nonspecific abdominal aortic aneurysm disease. Ann Vasc Surg. 1991 May;5(3):229-33. doi: 10.1007/BF02329378. PMID: 2064915.
  14. Kjeldsen L, Cowland JB, Borregaard N. Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse. Biochim Biophys Acta. 2000 Oct 18;1482(1-2):272-83. doi: 10.1016/s0167-4838(00)00152-7. PMID: 11058768.
  15. Wilson WR, Anderton M, Schwalbe EC, Jones JL, Furness PN, Bell PR, Thompson MM. Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture. Circulation. 2006 Jan 24;113(3):438-45. doi: 10.1161/CIRCULATIONAHA.105.551572. PMID: 16432074.
  16. Fontaine V, Jacob MP, Houard X, Rossignol P, Plissonnier D, Angles-Cano E, Michel JB. Involvement of the mural thrombus as a site of protease release and activation in human aortic aneurysms. Am J Pathol. 2002 Nov;161(5):1701-10. doi: 10.1016/S0002-9440(10)64447-1. PMID: 12414517; PMCID: PMC1850780.
  17. Ramos-Mozo P, Madrigal-Matute J, Vega de Ceniga M, Blanco-Colio LM, Meilhac O, Feldman L, Michel JB, Clancy P, Golledge J, Norman PE, Egido J, Martin-Ventura JL. Increased plasma levels of NGAL, a marker of neutrophil activation, in patients with abdominal aortic aneurysm. Atherosclerosis. 2012 Feb;220(2):552-6. doi: 10.1016/j.atherosclerosis.2011.11.023. Epub 2011 Nov 25. PMID: 22169111.
  18. Bartoli MA, Parodi FE, Chu J, Pagano MB, Mao D, Baxter BT, Buckley C, Ennis TL, Thompson RW. Localized administration of doxycycline suppresses aortic dilatation in an experimental mouse model of abdominal aortic aneurysm. Ann Vasc Surg. 2006 Mar;20(2):228-36. doi: 10.1007/s10016-006-9017-z. Epub 2006 Mar 30. PMID: 16572291.
  19. Appleton ND, Bailey DM, Morris-Stiff G, Lewis MH. Neutrophil to lymphocyte ratio predicts perioperative mortality following open elective repair of abdominal aortic aneurysms. Vasc Endovascular Surg. 2014 May;48(4):311-6. doi: 10.1177/1538574413519713. Epub 2014 Jan 24. PMID: 24464606.
  20. Aurelian SV, Adrian M, Andercou O, Bruno S, Alexandru O, Catalin T, Dan B. Neutrophil-to-Lymphocyte Ratio: A Comparative Study of Rupture to Nonruptured Infrarenal Abdominal Aortic Aneurysm. Ann Vasc Surg. 2019 Jul;58:270-275. doi: 10.1016/j.avsg.2018.11.026. Epub 2019 Feb 13. PMID: 30769065.
  21. Kordzadeh A, Malietzis G, Browne T, Prionidis I, Panayiotopoulos YP. Neutrophil to lymphocyte ratio (NLR) of five predicts 30-day morbidity in ruptured abdominal aortic aneurysms (rAAA): a retrospective cohort study. Int J Surg. 2015 Mar;15:45-8. doi: 10.1016/j.ijsu.2015.01.013. Epub 2015 Jan 30. PMID: 25641718.


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