Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous experimental studies have demonstrated that MMPs (matrix metalloproteinases) contribute to LV (left ventricular) remodelling. We hypothesized that cardiac MMPs are activated in patients with AMI (acute myocardial infarction) and, if so, MMP production may be attenuated by statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) through their cardiovascular protective actions. We studied 30 patients, ten control patients with stable angina pectoris and 20 patients with AMI, in whom LV catheterization at the chronic stage was performed 22+/-12 days (value is mean+/-S.D.) after the onset of AMI. Blood samples were collected from the CS (coronary sinus) and a peripheral artery. In patients with AMI, the levels of MMP-2 and MMP-9 were significantly (P<0.05) higher in the CS than the peripheral artery (MMP-2, 853+/-199 compared with 716+/-127 ng/ml; MMP-9, 165+/-129 compared with 98+/-82 ng/ml), whereas no significant differences were observed in the patients with angina pectoris. The CS-arterial concentration gradients of MMP-2 and MMP-9 correlated positively with BNP (brain natriuretic peptide) levels (MMP-2, R=0.68, P<0.01; MMP-9, R=0.59, P<0.05) and LV end-diastolic volume index (MMP-2, R=0.70, P<0.01; MMP-9, R=0.70, P<0.01). When patients with AMI treated with 10 mg of pravastatin or without (n=10 in each group) were compared, this statin therapy significantly (P<0.05) decreased the CS-arterial concentration gradients of MMP-2 (69+/-43 compared with 213+/-185 ng/ml) and MMP-9 (14+/-27 compared with 119+/-84 ng/ml). In conclusion, the enhanced production of cardiac MMP-2 and MMP-9 is associated with LV enlargement and elevated BNP levels in patients with AMI. A pleiotropic effect of statins appears to be associated with the modulation of cardiac MMP activation, which may be potentially beneficial in the attenuation of post-infarction LV remodelling.
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PMID:Enhanced cardiac production of matrix metalloproteinase-2 and -9 and its attenuation associated with pravastatin treatment in patients with acute myocardial infarction. 1693 10

Background Because systemic inflammation and endothelial dysfunction lead to heart failure with preserved ejection fraction, we characterized plasma levels of inflammatory and cardiac remodeling biomarkers in patients with Fabry disease ( FD ). Methods and Results Plasma biomarkers were studied in multicenter cohorts of patients with FD (n=68) and healthy controls (n=40). Plasma levels of the following markers of inflammation and cardiac remodeling were determined: tumor necrosis factor ( TNF ), TNF receptor 1 ( TNFR 1) and 2 ( TNFR 2), interleukin-6, matrix metalloprotease-2 ( MMP -2), MMP -8, MMP -9, galectin-1, galectin-3, B-type natriuretic peptide ( BNP ), midregional pro-atrial natriuretic peptide ( MR -pro ANP ), and globotriaosylsphingosine. Clinical profile, cardiac magnetic resonance imaging, and echocardiogram were reviewed and correlated with biomarkers. Patients with FD had elevated plasma levels of BNP , MR -pro ANP , MMP -2, MMP -9, TNF , TNFR 1, TNFR 2, interleukin-6, galectin-1, globotriaosylsphingosine, and analogues. Plasma TNFR 2, TNF , interleukin-6, MMP -2, and globotriaosylsphingosine were elevated in FD patients with left ventricular hypertrophy, whereas diastolic dysfunction correlated with higher BNP , MR -pro ANP , and MMP -2 levels. Patients with late gadolinium enhancement on cardiac magnetic resonance imaging had greater levels of BNP , MR -pro ANP , TNFR 1, TNFR 2, and MMP -2. Plasma BNP , MR -pro ANP , MMP -2, MMP -8, TNF , TNFR 1, TNFR 2, galectin-1, and galectin-3 were elevated in patients with renal dysfunction. Patients undergoing enzyme replacement therapy who have more severe disease had higher MMP -2, TNF , TNFR 1, TNFR 2, and globotriaosylsphingosine analogue levels. Conclusions Inflammatory and cardiac remodeling biomarkers are elevated in FD patients and correlate with disease progression. These features are consistent with a phenotype dominated by heart failure with preserved ejection fraction and suggest a key pathogenic role of systemic inflammation in FD .
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PMID:Elevated Inflammatory Plasma Biomarkers in Patients With Fabry Disease: A Critical Link to Heart Failure With Preserved Ejection Fraction. 3057 80