Plasma levels of active extracellular matrix metalloproteinases 2 and 9 in patients with essential hypertension before and after antihypertensive treatment

Abstract

This study was designed to test the hypothesis that plasma concentrations of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two enzymes that share similar substrate specificity (collagen type IV and V), possibly related to vascular remodelling, are altered in essential hypertension. The second aim of the study was to assess whether chronic antihypertensive treatment with the calcium channel blocker amlodipine would normalize these alterations. To test this hypothesis, we measured plasma concentrations of active MMP-2 and MMP-9 in 42 patients with never-treated essential hypertension and in 25 normotensive control subjects. Measurements were repeated after 6 months of treatment with the calcium channel blocker amlodipine. Baseline values of MMP-2 and MMP-9 were decreased (P ¼ 0.01 and 0.002, respectively) in hypertensive patients compared with normotensives. Hypertensive patients with systemic vascular resistances o1440 dyn s/cm 5 exhibited higher values of MMP-2 (P ¼ 0.005) and MMP-9 (P ¼ 0.001) than hypertensive patients with systemic vascular resistances 41440 dyn s/cm 5 . Treated patients attained a nonsignificant increase in MMP-2 plasma concentrations, but a significant increase in MMP-9 plasma concentrations (P ¼ 0.01) compared to respective values before treatment. In conclusion, these findings suggest that plasma concentrations of active MMP-2 and MMP-9, mainly related to vascular extracellular matrix metabolism, are depressed in patients with essential hypertension. A 6 month treatment with amlodipine can normalize MMP-9 but not MMP-2 plasma concentrations. The hypothesis that antihypertensive treatment may modulate collagen metabolism remains to be determined by further studies.

Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

“…However, they allow maintenance of pregnancy and promote an increased gestational age of delivery, thus decreasing adverse maternal and fetal outcomes. 31 In this respect, while some antihypertensive drugs can downregulate MMPs' activities [32][33][34][35] and as this effect may contribute to the reduction of blood pressure, no previous study had examined whether MMP-9 polymorphisms affect the antihypertensive effects of drugs used to treat hypertensive disorders of pregnancy. In this study, we investigated for the first time the effects of MMP-9 polymorphisms in responsiveness to methyldopa or to total antihypertensive therapy in hypertensive disorders of pregnancy.…”

Endothelial dysfunction is associated with increased levels of biomarkers in essential hypertension

“…5,10,11 The impaired endothelial function is closely linked with increased oxidative stress, 11,12 inflammation, remodelling and atherogenesis. 9 In this view, several acute-phase reactants, soluble adhesion molecules, chemokines and metalloproteinases are altered in patients at risk of cardiovascular events, such as hypertensives, [13][14][15][16][17] diabetics 18 or those with left ventricular hypertrophy. 19,20 Moreover, in patients with coronary heart disease some of these serum markers have prognostic implications.…”

Hydroxysafflor yellow A attenuates left ventricular remodeling after pressure overload-induced cardiac hypertrophy in rats

“…Matrix metalloproteinases (MMPs) belong to a family of structurally related zinc-containing endopeptidases, which are important in the degradation of extracellular matrix (ECM) components (Creemers et al, 2001) hypertension (Derosa et al, 2006;Zervoudaki et al, 2003). Broad-spectrum pharmacological inhibition of MMPs significantly attenuates myocardial remodeling associated with chronic volume overload, hypertension, myocardial infarction and other conditions in animal models (Chancey et al, 2002).…”