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Circulating matrix metalloproteinases and their endogenous inhibitors in patients with erectile dysfunction

Abstract

Erectile dysfunction (ED) may reflect vascular alterations associated with imbalanced matrix metalloproteinases (MMPs) activities. However, no previous study has compared MMPs levels in ED patients with those found in healthy subjects. We measured the circulating MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in ED patients, with or without diabetes mellitus (DM), and in healthy controls. We studied 28 healthy men (control group), 35 men with ED (ED group), and 33 men with ED and DM (ED/DM group). MMP-2, MMP-9, TIMP-1 and TIMP-2 plasma levels were measured by enzyme-linked immunosorbent assay and zymography. We found no differences in MMP-9 levels (P>0.05) among groups. However, while patients in the ED group had similar TIMP-1 levels compared with those found in the control group, we found higher TIMP-1 levels and lower MMP-9/TIMP-1 ratios in the ED/DM group compared with controls (P<0.05). While both groups of patients (ED and ED/DM) had slightly lower MMP-2 levels compared with controls (P<0.05), we found no differences in TIMP-2 levels among the study groups (P>0.05), and no differences in MMP-2/TIMP-2 ratios (P>0.05). We found evidence indicating lack of significant alterations in circulating net MMP-9 and MMP-2 activities in patients with ED, and lower net MMP-9 activity in diabetic patients with ED.

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References

  1. McVary KT . Clinical practice. Erectile dysfunction. N Engl J Med 2007; 357: 2472–2481.

    Article  CAS  Google Scholar 

  2. Chew KK, Finn J, Stuckey B, Gibson N, Sanfilippo F, Bremner A et al. Erectile dysfunction as a predictor for subsequent atherosclerotic cardiovascular events: findings from a linked-data study. J Sex Med 2010; 7: 192–202.

    Article  Google Scholar 

  3. Hale TM, Hannan JL, Carrier S, deBlois D, Adams MA . Targeting vascular structure for the treatment of sexual dysfunction. J Sex Med 2009; 6 (Suppl 3): 210–220.

    Article  Google Scholar 

  4. Fung MM, Bettencourt R, Barrett-Connor E . Heart disease risk factors predict erectile dysfunction 25 years later: the Rancho Bernardo Study. J Am Coll Cardiol 2004; 43: 1405–1411.

    Article  Google Scholar 

  5. Sullivan ME, Keoghane SR, Miller MA . Vascular risk factors and erectile dysfunction. BJU Int 2001; 87: 838–845.

    Article  CAS  Google Scholar 

  6. Selvin E, Burnett AL, Platz EA . Prevalence and risk factors for erectile dysfunction in the US. Am J Med 2007; 120: 151–157.

    Article  Google Scholar 

  7. Kloner R . Erectile dysfunction and hypertension. Int J Impot Res 2007; 19: 296–302.

    Article  CAS  Google Scholar 

  8. Aversa A, Bruzziches R, Francomano D, Natali M, Gareri P, Spera G . Endothelial dysfunction and erectile dysfunction in the aging man. Int J Urol 2010; 17: 38–47.

    Article  Google Scholar 

  9. Schwartz BG, Kloner RA . How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors. Int J Impot Res 2009; 21: 327–335.

    Article  CAS  Google Scholar 

  10. Cho NH, Ahn CW, Park JY, Ahn TY, Lee HW, Park TS et al. Prevalence of erectile dysfunction in Korean men with Type 2 diabetes mellitus. Diabet Med 2006; 23: 198–203.

    Article  CAS  Google Scholar 

  11. Ma RC, So WY, Yang X, Yu LW, Kong AP, Ko GT et al. Erectile dysfunction predicts coronary heart disease in type 2 diabetes. J Am Coll Cardiol 2008; 51: 2045–2050.

    Article  Google Scholar 

  12. Bouvet C, Gilbert LA, Girardot D, deBlois D, Moreau P . Different involvement of extracellular matrix components in small and large arteries during chronic NO synthase inhibition. Hypertension 2005; 45: 432–437.

    Article  CAS  Google Scholar 

  13. Castro MM, Rizzi E, Figueiredo-Lopes L, Fernandes K, Bendhack LM, Pitol DL et al. Metalloproteinase inhibition ameliorates hypertension and prevents vascular dysfunction and remodeling in renovascular hypertensive rats. Atherosclerosis 2008; 198: 320–331.

    Article  CAS  Google Scholar 

  14. Castro MM, Rizzi E, Prado CM, Rossi MA, Tanus-Santos JE, Gerlach RF . Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases in hypertensive vascular remodeling. Matrix Biol 2010; 29: 194–201.

    Article  CAS  Google Scholar 

  15. Rizzi E, Castro MM, Prado CM, Silva CA, Fazan Jr R, Rossi MA et al. Matrix metalloproteinase inhibition improves cardiac dysfunction and remodeling in 2-kidney, 1-clip hypertension. J Card Fail 2010; 16: 599–608.

    Article  CAS  Google Scholar 

  16. Raffetto JD, Khalil RA . Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 2008; 75: 346–359.

    Article  CAS  Google Scholar 

  17. Chow AK, Cena J, Schulz R . Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature. Brit J Pharmacol 2007; 152: 189–205.

    Article  CAS  Google Scholar 

  18. Schulz R . Intracellular targets of matrix metalloproteinase-2 in cardiac disease: rationale and therapeutic approaches. Annu Rev Pharmacol Toxicol 2007; 47: 211–242.

    Article  CAS  Google Scholar 

  19. Derosa G, D’Angelo A, Tinelli C, Devangelio E, Consoli A, Miccoli R et al. Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in diabetic and healthy subjects. Diabetes Metab 2007; 33: 129–134.

    Article  CAS  Google Scholar 

  20. Martins-Oliveira A, Speciali JG, Dach F, Marcaccini AM, Goncalves FM, Gerlach RF et al. Different circulating metalloproteinases profiles in women with migraine with and without aura. Clin Chim Acta 2009; 408: 60–64.

    Article  CAS  Google Scholar 

  21. Palei AC, Sandrim VC, Cavalli RC, Tanus-Santos JE . Comparative assessment of matrix metalloproteinase (MMP)-2 and MMP-9, and their inhibitors, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in preeclampsia and gestational hypertension. Clin Biochem 2008; 41: 875–880.

    Article  CAS  Google Scholar 

  22. Cappelleri JC, Rosen RC, Smith MD, Mishra A, Osterloh IH . Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function. Urology 1999; 54: 346–351.

    Article  CAS  Google Scholar 

  23. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A . The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822–830.

    Article  CAS  Google Scholar 

  24. Gerlach RF, Demacq C, Jung K, Tanus-Santos JE . Rapid separation of serum does not avoid artificially higher matrix metalloproteinase (MMP)-9 levels in serum versus plasma. Clin Biochem 2007; 40: 119–123.

    Article  CAS  Google Scholar 

  25. Gerlach RF, Meschiari CA, Marcaccini AM, Palei AC, Sandrim VC, Cavalli RC et al. Positive correlations between serum and plasma matrix metalloproteinase (MMP)-2 or MMP-9 levels in disease conditions. Clin Chem Lab Med 2009; 47: 888–891.

    Article  CAS  Google Scholar 

  26. Makowski GS, Ramsby ML . Identification and partial characterization of three calcium- and zinc-independent gelatinases constitutively present in human circulation. Biochem Mol Biol Int 1998; 46: 1043–1053.

    CAS  PubMed  Google Scholar 

  27. Martinez ML, Lopes LF, Coelho EB, Nobre F, Rocha JB, Gerlach RF et al. Lercanidipine reduces matrix metalloproteinase-9 activity in patients with hypertension. J Cardiovasc Pharmacol 2006; 47: 117–122.

    Article  CAS  Google Scholar 

  28. Belo VA, Souza-Costa DC, Lana CM, Caputo FL, Marcaccini AM, Gerlach RF et al. Assessment of matrix metalloproteinase (MMP)-2, MMP-8, MMP-9, and their inhibitors, the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in obese children and adolescents. Clin Biochem 2009; 42: 984–990.

    Article  CAS  Google Scholar 

  29. Goncalves FM, Jacob-Ferreira AL, Gomes VA, Casella-Filho A, Chagas AC, Marcaccini AM et al. Increased circulating levels of matrix metalloproteinase (MMP)-8, MMP-9, and pro-inflammatory markers in patients with metabolic syndrome. Clin Chim Acta 2009; 403: 173–177.

    Article  CAS  Google Scholar 

  30. Hu J, Van den Steen PE, Sang QX, Opdenakker G . Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 2007; 6: 480–498.

    Article  CAS  Google Scholar 

  31. Spinale FG . Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 2007; 87: 1285–1342.

    Article  CAS  Google Scholar 

  32. Bonnema DD, Webb CS, Pennington WR, Stroud RE, Leonardi AE, Clark LL et al. Effects of age on plasma matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). J Card Fail 2007; 13: 530–540.

    Article  CAS  Google Scholar 

  33. Guedez L, McMarlin AJ, Kingma DW, Bennett TA, Stetler-Stevenson M, Stetler-Stevenson WG . Tissue inhibitor of metalloproteinase-1 alters the tumorigenicity of Burkitt's lymphoma via divergent effects on tumor growth and angiogenesis. Am J Pathol 2001; 158: 1207–1215.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  35. Fontana V, Silva PS, Belo VA, Antonio RC, Ceron CS, Biagi C et al. Consistent alterations of circulating matrix metalloproteinases levels in untreated hypertensives and in spontaneously hypertensive rats: a relevant pharmacological target. Basic Clin Pharmacol Toxicol 2011; 109: 130–137.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior.

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Correspondence to J E Tanus-Santos.

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Muniz, J., Lacchini, R., Belo, V. et al. Circulating matrix metalloproteinases and their endogenous inhibitors in patients with erectile dysfunction. Int J Impot Res 24, 38–43 (2012). https://doi.org/10.1038/ijir.2011.44

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