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Matrix metalloproteinase-9 polymorphism contributes to blood pressure and arterial stiffness in essential hypertension

Journal of Human Hypertension volume 21, pages 861–867 (2007)Cite this article

Abstract

Arterial stiffness is an independent predictor of cardiovascular events in a hypertensive population. Serum levels of matrix metalloproteinase (MMP)-9 are associated with arterial stiffness and predict cardiovascular risk. We investigated the role of MMP-9 polymorphism −1562C>T on blood pressure (BP) and arterial stiffness in a newly diagnosed hypertensive population. Untreated hypertensive patients (n=215, mean age 46±13 years) were studied. Supine BP, carotid-femoral pulse wave velocity (PWV) and augmentation index were assessed. Serum biochemistry and plasma MMP-9 concentrations were measured and genotyping performed following extraction of genomic DNA. BP, aortic PWV and serum MMP-9 levels were significantly higher in T-allele carriers of the −1562C>T polymorphism with a significant gene–dose effect (P<0.0001). In a stepwise regression model adjusting for known or likely determinants, the 1562C>T polymorphism emerged as an independent predictor of systolic BP (R2=0.25, P<0.0001), diastolic BP (R2=0.16, P<0.0001) and PWV (R2=0.47,P<0.0001). This is the first study to show the effect of MMP-9 polymorphism on BP and aortic stiffness in a hypertensive population. These results suggest that hypertensive patients carrying the T allele may be at increased risk of cardiovascular events.

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References

  1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J . Global burden of hypertension. Lancet 2005; 365: 217–223.

    Article  Google Scholar 

  2. Willum-Hansen T, Staessen JA, Torp-Pedersen C, Rasmussen S, Thijs L, Ibsen H et al. Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation 2006; 113: 664–670.

    Article  Google Scholar 

  3. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37: 1236–1241.

    Article  CAS  Google Scholar 

  4. Laurent S, Katsahian S, Fassot C, Tropeano AI, Gautier I, Laloux B et al. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke 2003; 34: 1–4.

    Article  Google Scholar 

  5. Boutouyrie P, Tropeano AI, Asmar R, Gautier I, Benetos A, Lacolley P et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002; 39: 10–15.

    Article  CAS  Google Scholar 

  6. Spinale FG . Matrix metalloproteinases: regulation and dysregulation in the failing heart. Circ Res 2002; 90: 520–530.

    Article  CAS  Google Scholar 

  7. Noji Y, Kajinami K, Kawashiri MA, Todo Y, Horita T, Nohara A et al. Circulating matrix metalloproteinases and their inhibitors in premature coronary atherosclerosis. Clin Chem Lab Med 2001; 39: 380–384.

    Article  CAS  Google Scholar 

  8. Longo GM, Xiong W, Griener TC, Zhao Y, Fiotti N, Baxter BT . Matrix metalloproteinase 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest 2002; 110: 625–632.

    Article  CAS  PubMed Central  Google Scholar 

  9. Zhang B, Ye S, Hermann SM, Erikssson P, de Matt M, Evans A et al. Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation 1999; 99: 1788–1794.

    Article  CAS  Google Scholar 

  10. Derosa G, D'Angelo A, Ciccarelli L, Piccini MN, Pricolo F, Salvadeo S et al. Matrix metalloproteinase-2, and 9 and tissue inhibitor of metalloproteinase-1 in patients with hypertension. Endothelium 2006; 13: 227–231.

    Article  CAS  Google Scholar 

  11. Marx N, Frolich JC, Siam L, Ittner J, Wierse G, Schmidt A et al. Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2003; 23: 283–288.

    Article  CAS  Google Scholar 

  12. Blankenberg S, Rupprecht HJ, Poirier O, Bickel C, Smieja M, Hafner G et al. Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 2003; 107: 1579–1585.

    Article  CAS  Google Scholar 

  13. Yasmin, Wallace S, McEniery CM, Dakham Z, Pusalkar P, Mak-Petaja K et al. Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are associated with systolic hypertension and arterial stiffness. Arterioscl Thromb Vasc Biol 2005; 25: 372.

    Article  CAS  Google Scholar 

  14. Morgan AR, Zhang B, Tapper W, Collins A, Ye S . Haplotypic analysis of the MMP-9 gene in relation to coronary artery disease. J Mol Med 2003; 81: 321–326.

    Article  CAS  Google Scholar 

  15. Medley TL, Cole TJ, Dart AM, Gatzka CD, Kingwell BA . Matrix metalloproteinase-9 genotype influences large artery stiffness through effects on aortic gene and protein expression. Arterioscl Thromb Vasc Biol 2004; 24: 1479–1484.

    Article  CAS  Google Scholar 

  16. Yasmin, McEniery C, O'Shaughnessy KM, Harnett P, Arshad A, Wallace S et al. Variation in the human matrix metalloproteinase-9 gene is associated with arterial stiffness in healthy individuals. Arterioscl Thromb Vasc Biol 2006; 26: 1799–1805.

    Article  CAS  Google Scholar 

  17. Mahmud A, Feely J . Arterial stiffness is related to systemic inflammation in essential hypertension. Hypertension 2005; 46: 1118–1122.

    Article  CAS  Google Scholar 

  18. Julius S, Shawna N . Sympathetic overactivity in hypertension. Am J Hypertens 1996; 9: 113S–120S.

    Article  CAS  Google Scholar 

  19. Laurent S, Boutouyrie P, Lacolley P . Structural and genetic bases of arterial stiffness. Hypertension 2006; 45: 1050–1055.

    Article  Google Scholar 

  20. McNulty M, Mahmud A, Spiers J, Feely J . Collagen type-I degradation is related to arterial stiffness in hypertensive and normotensive subjects. J Hum Hypertens 2006; 20: 867–873.

    Article  CAS  PubMed Central  Google Scholar 

  21. Galis ZS, Johnson C, Godin D, Magid R, Shipley MJ, Senior RM et al. Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ Res 2002; 91: 852–859.

    Article  CAS  PubMed Central  Google Scholar 

  22. Skalska A, Gasowski J, Cwynar M . The relationship between pulse wave velocity and indexes of collagen synthesis in hypertensive patients, according to the level of systolic blood pressure. J Hum Hypertens 2005; 19: 731–735.

    Article  CAS  Google Scholar 

  23. Gearing AJH, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson JH et al. Processing of tumour necrosis factor-a precursor by metalloproteinases. Nature 1994; 30: 555–557.

    Article  Google Scholar 

  24. Schonbeck U, Mach F, Libby P . Generation of biologically active IL-1b by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1b processing. J Immunol 1998; 161: 3340–3346.

    CAS  PubMed  Google Scholar 

  25. Kelly RP, Millasseau SC, Ritter JM, Chowienczyk PJ . Vasoactive drugs influence aortic augmentation index independently of pulse wave velocity in healthy men. Hypertension 2001; 37: 1429–1433.

    Article  CAS  Google Scholar 

  26. Mahmud A, Feely J . Adiponectin and arterial stiffness. Am J Hypertens 2005; 18: 1543–1548.

    Article  CAS  Google Scholar 

  27. Cowley Jr AW . The genetic dissection of essential hypertension. Nat Genet 2006; 7: 829–840.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Trinity College Dublin, Dublin, Ireland

    S Zhou, J Feely, J P Spiers & A Mahmud

  2. Hypertension Clinic, St James's Hospital, Dublin, Ireland

    J Feely & A Mahmud

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  1. S Zhou
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  2. J Feely
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  3. J P Spiers
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  4. A Mahmud
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Correspondence to A Mahmud.

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Zhou, S., Feely, J., Spiers, J. et al. Matrix metalloproteinase-9 polymorphism contributes to blood pressure and arterial stiffness in essential hypertension. J Hum Hypertens 21, 861–867 (2007). https://doi.org/10.1038/sj.jhh.1002244

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  • DOI: https://doi.org/10.1038/sj.jhh.1002244

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