ORIGINAL ARTICLE Circulating matrix metalloproteinases and their endogenous inhibitors in patients with erectile dysfunction JJ Muniz 1 , R Lacchini 1 , VA Belo 1 , YTDA Nobre 2 , S Tucci Jr 2 , ACP Martins 2 and JE Tanus-Santos 3 1 Department of Pharmacology, State University of Campinas, Campinas, SP, Brazil; 2 Department of Surgery and Anatomy, Faculty of Medicine of Ribeirao Preto, RibeiraoPreto, SP, Brazil and 3 Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil 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 (P40.05) 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 (Po0.05). While both groups of patients (ED and ED/DM) had slightly lower MMP-2 levels compared with controls (Po0.05), we found no differences in TIMP-2 levels among the study groups (P40.05), and no differences in MMP-2/TIMP- 2 ratios (P40.05). 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. International Journal of Impotence Research (2012) 24, 38–43; doi:10.1038/ijir.2011.44; published online 15 September 2011 Keywords: erectile dysfunction; matrix metalloproteinases; tissue inhibitors of metalloproteinases Introduction Erectile dysfunction (ED) is a clinical condition affecting millions of men worldwide, and is attribu- table to different causes including neurological, hormonal, psychological and vascular problems. 1,2 However, vascular dysfunction has a major role in this condition, and it is now clear that ED may reflect vascular functional and structural alterations found in cardiovascular diseases. 1–3 Indeed, ED shares many risk factors with cardiovascular dis- eases 4–7 and it may be an early manifestation of vascular dysfunction, 8 and possibly a clinical marker for cardiovascular diseases. 2,9 Moreover, ED is very common among men with diabetes mellitus (DM), 4–6,10,11 in whom the prevalence has been reported to vary from 20–71%. 10 Recent studies have implicated matrix metallo- proteinases (MMPs) as key players in the functional and structural cardiovascular alterations associated with hypertension 12–15 and with other cardiovascu- lar diseases. 16,17 Although MMPs are widely known to degrade the components of the extracellular matrix, they also have many other roles that are now being widely studied, especially in the cardi- ovascular system. 17,18 However, although imbal- anced MMPs activities may underlie the vascular alterations of many cardiovascular diseases, there is no study examining the hypothesis that patients with ED have imbalanced levels of MMPs. In addition, while there is evidence showing increased MMPs levels in DM, 19 there is no study comparing MMPs levels in diabetic and nondiabetic patients with ED. In the present study, we hypothesized that altered MMPs concentrations would be found in patients with ED, especially in patients with ED and DM, compared with healthy controls. Therefore, we studied the circulating MMP-2 and MMP-9 levels Received 18 March 2011; revised 24 May 2011; accepted 10 August 2011; published online 15 September 2011 Correspondence: Dr JE Tanus-Santos, Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049- 900 Ribeirao Preto, SP, Brazil. E-mail: tanus@fmrp.usp.br or tanussantos@yahoo.com International Journal of Impotence Research (2012) 24, 38–43 & 2012 Macmillan Publishers Limited All rights reserved 0955-9930/12 www.nature.com/ijir