Metalloproteinase inhibition ameliorates hypertension and prevents vascular dysfunction and remodeling in renovascular hypertensive rats

Castro, Michele M.; Rizzi, Élen; Figueiredo-Lopes, Lívia; Fernandes, Karin Sá; Bendhack, Lusiane Maria; Pitol, Dimítrius Leonardo; Gerlach, Raquel Fernanda; Tanus‐Santos, Jose E.

doi:10.1016/j.atherosclerosis.2007.10.011

Cited by 186 publications

(187 citation statements)

References 42 publications

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“…Moreover, increased MMP-2 levels may contribute to vascular dysfunction (Castro et al, 2008(Castro et al, , 2010 secondary to hypertension-related mechanical stress on the vascular wall (Donnelly et al, 2003). Therefore, although we have not assessed vascular MMP-2 levels in the present study, the higher MMP-2/TIMP-2 ratios that we found in gestational hypertension may well reflect these mechanisms.…”

Section: Discussionmentioning

confidence: 71%

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

Palei

Sandrim

Amaral

et al. 2012

Experimental and Molecular Pathology

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Section: Discussionmentioning

confidence: 71%

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

Palei

Sandrim

Amaral

et al. 2012

Experimental and Molecular Pathology

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“…To our knowledge, no previous study has examined whether MMP-2 polymorphisms or haplotypes are associated with hypertension, although experimental evidence has implicated MMP-2 in the pathogenesis of hypertension [24][25][26][27] and in hypertensive LVH. 8 Previous studies suggest that genetic polymorphisms modify MMP-2 expression or activity.…”

Section: Discussionmentioning

confidence: 99%

Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients

et al. 2011

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Matrix metalloproteinases (MMPs) are involved in cardiac remodelling. We examined whether MMP-2 genetic polymorphisms are associated with hypertension and left ventricular (LV) remodelling in hypertensive patients. We studied 160 hypertensive patients and 123 healthy controls. Echocardiography was performed in all patients and the C À1306 T (rs243865) and C À735 T (rs 2285053) MMP-2 polymorphisms were analysed. Haplo.stats analysis was used to evaluate whether MMP-2 haplotypes are associated with hypertension and with extremes in LV mass index (LVMI). Multiple linear regression analysis was performed to assess whether MMP-2 genotypes or haplotypes affect LVMI and other echocardiography parameters. The C À1306 T 'CC' genotype was associated with reduced LVMI and LV end-diastolic diameter (EDD) (P ¼ 0.0365 and P ¼ 0.0438, respectively). The haplotype 'C, C' was associated with reduced LVMI and EDD (P ¼ 0.0278 and P ¼ 0.0322, respectively). The comparison of upper and lower extremes of the LVMI phenotype showed that the 'C, C' haplotype was more common in the lower LVMI group (P ¼ 0.0060), whereas the 'T, C' haplotype was more common in the higher quartile of LVMI (P ¼ 0.0187), and this haplotype was associated with increased risk of higher LVMI values (odds ratio ¼ 3.5121, 95% confidence interval ¼ 1.3193-9.3494). The findings suggest that MMP-2 polymorphisms affect hypertension-induced LV remodelling.

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“…Imbalanced MMPs activities have been implicated in many clinical cardiovascular diseases, [12][13][14][15][16][17][18]27 and the use of MMPs inhibitors has been suggested as a relevant pharmacological target, especially to prevent the vascular alterations associated with these conditions. 12,13,[28][29][30] While there is evidence that MMPs in erectile dysfunction JJ Muniz et al patients with ED are more likely to have the vascular alterations commonly found in cardiovascular diseases, 2,4-9 especially among diabetics, 4-6,10,11 our findings showed similar net MMP-2 and MMP-9 activities in ED patients and in healthy controls, thus suggesting that these enzymes may not be involved in ED.…”

Section: Discussionmentioning

confidence: 99%

“…2,9 Moreover, ED is very common among men with diabetes mellitus (DM), [4][5][6]10,11 in whom the prevalence has been reported to vary from 20-71%. 10 Recent studies have implicated matrix metalloproteinases (MMPs) as key players in the functional and structural cardiovascular alterations associated with hypertension [12][13][14][15] and with other cardiovascular 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 cardiovascular system.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we studied the circulating MMP-2 and MMP-9 levels (which are the very relevant MMPs in the pathogenesis of cardiovascular diseases [12][13][14][15][16][17][18] ) in ED patients with or without DM, and in healthy controls. In addition, we have also assessed the circulating levels of major MMPs endogenous inhibitors, the tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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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.

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Metalloproteinase inhibition ameliorates hypertension and prevents vascular dysfunction and remodeling in renovascular hypertensive rats

Cited by 186 publications

References 42 publications

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients

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

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