MMP-2, MMP-9, and TIMP-4 and Response to Aspirin in Diabetic and Nondiabetic Patients with Stable Coronary Artery Disease: A Pilot Study

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2017 Aug 4

PMID 28770228

Citations 10

Authors

Wiktor Kuliczkowski

Marek Radomski

Mariusz Gasior

Joanna Urbaniak

Jacek Kaczmarski

Andrzej Mysiak

Marta Negrusz-Kawecka

Iwona Bil-Lula

Affiliations

Soon will be listed here.

Abstract

Background: High on-aspirin treatment platelets reactivity (HPR) is a significant problem in long-term secondary prevention of cardiovascular events. We hypothesize that imbalance between platelets MMPs/TIMPs results in cardiovascular disorders. We also explored whether chronically elevated blood glucose affects MMP-2/TIMP-4 release from platelets.

Materials And Methods: Seventy patients with stable coronary artery disease, supplemented with aspirin, participated in this pilot study. The presence of HPR and/or diabetes mellitus was considered as the differentiating factor. Light aggregometry, impedance aggregometry, and ELISA tests for TXB2, MMP-2, MMP-9, and TIMP-4 were performed in serum, plasma, platelet-rich plasma, and platelets-poor plasma, as appropriate.

Results: Aspirin-HPR did not affect plasma MMP-2, MMP-9, and TIMP-4. Arachidonic acid-induced aggregation of platelets from aspirin-HPR patients did not lead to increased release of MMP-2, MMP-9, and TIMP-4. Studying patients at the lowest TXB2 serum concentration quartile revealed that high concentration of plasma TIMP-4 and TIMP-4 negatively correlated with TXB2 and platelet aggregation. Diabetics showed an increased plasma MMP-2 as well as an increased MMP-2 in supernatants after platelet aggregation. However, diabetes mellitus did not affect MMP-9 and TIMP-4.

Conclusion: Aspirin-HPR did not affect the translocation and release of MMPs and TIMP-4 from platelets. TIMP-4 may serve as a marker of TXA2-mediated platelet aggregation. Chronically elevated plasma glucose increases plasma MMP-2, and HPR potentiates this phenomenon.

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References

Rauzi F, Kirkby N, Edin M, Whiteford J, Zeldin D, Mitchell J . Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1. FASEB J. 2016; 30(12):4256-4266. PMC: 5102123. DOI: 10.1096/fj.201600530R. View

Sawicki G, Salas E, MURAT J, Radomski M . Release of gelatinase A during platelet activation mediates aggregation. Nature. 1997; 386(6625):616-9. DOI: 10.1038/386616a0. View

Signorelli S, Malaponte G, Libra M, Di Pino L, Celotta G, Bevelacqua V . Plasma levels and zymographic activities of matrix metalloproteinases 2 and 9 in type II diabetics with peripheral arterial disease. Vasc Med. 2005; 10(1):1-6. DOI: 10.1191/1358863x05vm582oa. View

Alameddine H, Morgan J . Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Inflammation and Fibrosis of Skeletal Muscles. J Neuromuscul Dis. 2016; 3(4):455-473. PMC: 5240616. DOI: 10.3233/JND-160183. View

Hu J, Van den Steen P, Sang Q, Opdenakker G . Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov. 2007; 6(6):480-98. DOI: 10.1038/nrd2308. View

Martin-Timon I, Sevillano-Collantes C, Segura-Galindo A, Del Canizo-Gomez F . Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?. World J Diabetes. 2014; 5(4):444-70. PMC: 4127581. DOI: 10.4239/wjd.v5.i4.444. View

Bhatt L, Veeranjaneyulu A . Enhancement of matrix metalloproteinase 2 and 9 inhibitory action of minocycline by aspirin: an approach to attenuate outcome of acute myocardial infarction in diabetes. Arch Med Res. 2014; 45(3):203-9. DOI: 10.1016/j.arcmed.2014.01.008. View

Kostov K, Blazhev A, Atanasova M, Dimitrova A . Serum Concentrations of Endothelin-1 and Matrix Metalloproteinases-2, -9 in Pre-Hypertensive and Hypertensive Patients with Type 2 Diabetes. Int J Mol Sci. 2016; 17(8). PMC: 5000590. DOI: 10.3390/ijms17081182. View

Dear M, Dani N, Parkinson W, Zhou S, Broadie K . Two classes of matrix metalloproteinases reciprocally regulate synaptogenesis. Development. 2015; 143(1):75-87. PMC: 4725201. DOI: 10.1242/dev.124461. View

10.

Si-Tayeb K, Monvoisin A, Mazzocco C, Lepreux S, Decossas M, Cubel G . Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis. Am J Pathol. 2006; 169(4):1390-401. PMC: 1780186. DOI: 10.2353/ajpath.2006.060005. View

11.

Rahat B, Sharma R, Bagga R, Hamid A, Kaur J . Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases. Reproduction. 2016; 152(1):11-22. DOI: 10.1530/REP-16-0060. View

12.

Parks W, Wilson C, Lopez-Boado Y . Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol. 2004; 4(8):617-29. DOI: 10.1038/nri1418. View

13.

Cattaneo M . High on-treatment platelet reactivity--definition and measurement. Thromb Haemost. 2013; 109(5):792-8. DOI: 10.1160/TH12-10-0758. View

14.

Santos-Martinez M, Medina C, Jurasz P, Radomski M . Role of metalloproteinases in platelet function. Thromb Res. 2007; 121(4):535-42. DOI: 10.1016/j.thromres.2007.06.002. View

15.

Salas E, Sawicki G, Wozniak M, Radomski M, Davidge S . Differential regulation of platelet aggregation by matrix metalloproteinases-9 and -2. Thromb Haemost. 1999; 82(6):1730-5. View

16.

Haffner S, Lehto S, Ronnemaa T, Pyorala K, Laakso M . Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998; 339(4):229-34. DOI: 10.1056/NEJM199807233390404. View

17.

Galis Z, Sukhova G, Lark M, Libby P . Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994; 94(6):2493-503. PMC: 330083. DOI: 10.1172/JCI117619. View

18.

Visse R, Nagase H . Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003; 92(8):827-39. DOI: 10.1161/01.RES.0000070112.80711.3D. View

19.

Abraham R, Schafer J, Rothe M, Bange J, Knyazev P, Ullrich A . Identification of MMP-15 as an anti-apoptotic factor in cancer cells. J Biol Chem. 2005; 280(40):34123-32. DOI: 10.1074/jbc.M508155200. View

20.

Nguyen T, Shynlova O, Lye S . Matrix Metalloproteinase Expression in the Rat Myometrium During Pregnancy, Term Labor, and Postpartum. Biol Reprod. 2016; 95(1):24. PMC: 5029434. DOI: 10.1095/biolreprod.115.138248. View