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Matrix Metalloproteinases Essay

1198 words - 5 pages

Matrix metalloproteinases are members of a large family of enzymes that can degrade extracellular matrix as well as other molecules [1]. MMPs participate in a broad variety of normal and pathologic states [2], and have been implicated as potential mediators of cardiac dilation and heart failure. Indeed, in culture cells [3,4], animal models mimicking the CHF syndrome [5,6] and CHF patients [7-9], a mechanistic relationship has been demonstrated respect to myocardial MMP expression and left ventricular (LV) remodeling process [3-9]. Likewise, recent reports on endothelial culture cells [10-12] and animal models of CHF [13,14] have shown that the increase of expression and activity of MMP-2 and MMP-9 (called gelatinases) might also play an important role in the impairement of endothelial function, a key event contributing on morbidity and mortality in CHF patients [15]. However, data respect to the role of MMPs on endothelial dysfunction in the setting of human CHF is completely unknown. Therefore, the aim of this study was to assess the association between the activity of gelatinases and endothelial dysfunction in patients with CHF. We hypothesized that a higher plasma MMP-2 and MMP-9 activities correlate with a lower endothelial function in patients with CHF.
We included CHF patients, NYHA functional class II-III controlled in a university clinical center. All patients signed an informed consent approved by our institutional Review Board and Ethics Committee. Inclusion criteria were left ventricular ejection fraction (LVEF) < 40%, measured by radionuclide ventriculography or echocardiogram, conventional pharmacological treatment including diuretics, β-blockers, digoxin and angiotensin-converting enzyme (ACE) inhibitors and stable clinical condition during the last four weeks. Exclusion criteria were acute coronary syndrome, coronary artery bypass surgery or coronary angioplasty in the last six months, uncontrolled arterial hypertension (systolic blood pressure > 160 mm Hg or diastolic blood pressure > 90 mm Hg), hypertrophic myocardiopathy and congenital cardiopathy, use of antioxidants in the previous two months and presence of other conditions that affect determination of MMPs activity and endothelial function status such as renal failure (plasma creatinine > 2.0 mg/dL), autoimmune diseases, neoplasia, advanced liver or pulmonary disease, and acute or chronic inflammation. Moreover, a group of healthy age-and-sex-matched volunteers were included. Subjects were ineligible as controls if they were taking any medications, vitamin supplements, antioxidants or if they drank alcohol on a regular basis. The activity of MMP-2 and -9 were measured by gel zymography in plasma samples as described by Bittner et al [16]. High-resolution ultrasound was used to measure changes in brachial artery diameter (FDD), according to the previously described technique [17]. Results were presented as mean ± SD for continuous variables and percentages for categorical...

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