Dataset Information

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure.

ABSTRACT: Heart failure (HF) is an acute or chronic clinical syndrome that results in a decrease in cardiac output and an increase in intracardiac pressure at rest or upon exertion. The pathophysiology of HF is heterogeneous and results from an initial harmful event in the heart that promotes neurohormonal changes such as autonomic dysfunction and activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, and inflammation. Cardiac remodeling occurs, which is associated with degradation and disorganized synthesis of extracellular matrix (ECM) components that are controlled by ECM metalloproteinases (MMPs). MMP-2 is part of this group of proteases, which are classified as gelatinases and are constituents of the heart. MMP-2 is considered a biomarker of patients with HF with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). The role of MMP-2 in the development of cardiac injury and dysfunction has clearly been demonstrated in animal models of cardiac ischemia, transgenic models that overexpress MMP-2, and knockout models for this protease. New research to minimize cardiac structural and functional alterations using non-selective and selective inhibitors for MMP-2 demonstrates that this protease could be used as a possible pharmacological target in the treatment of HF.

SUBMITTER: Goncalves PR

PROVIDER: S-EPMC9331741 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure.

Gonçalves Pricila Rodrigues PR Nascimento Lisandra Duarte LD Gerlach Raquel Fernanda RF Rodrigues Keuri Eleutério KE Prado Alejandro Ferraz AF

Pharmaceuticals (Basel, Switzerland) 20220725 8

Heart failure (HF) is an acute or chronic clinical syndrome that results in a decrease in cardiac output and an increase in intracardiac pressure at rest or upon exertion. The pathophysiology of HF is heterogeneous and results from an initial harmful event in the heart that promotes neurohormonal changes such as autonomic dysfunction and activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, and inflammation. Cardiac remodeling occurs, which is associated with degradati ...[more]

PMID: 35893744

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Project description:In cardiovascular disorders, the myocardium may be subjected to the breakdown and remodeling of collagen by metalloproteinase-9 (MMP-9). We hypothesized that the serum MMP-9 concentration may be elevated in pediatric patients with rheumatic heart disease (RHD) and heart failure (HF), and its level can be correlated with the HF severity. Thus, in the present study, we aimed to evaluate the sensitivity and accuracy of MMP-9 to predict HF in children with RHD and to determine its effectiveness as an indicator of the degree of HF. This study included 98 consecutive children admitted to the Department of Pediatrics, Zagazig University Hospital, Al Sharqia Governorate, Egypt with newly diagnosed RHD. Their ages ranged from 8.5 to 16 years. Fifty-eight children had RHD without HF while 40 children were complicated with HF which was diagnosed clinically and by echocardiography. A total of 44 healthy children were enrolled as a control group. MMP-9 serum levels were estimated by enzyme-linked immunosorbent assay. The serum MMP-9 concentration was higher in the RHD without HF and RHD with HF groups than this level noted in the control (P<0.001). MMP-9 was a significant predictor of HF; area under the curve (AUC)=0.85 [95% confidence interval (CI), 0.76-0.94]. At the level of 386.9 ng/ml, MMP-9 detected HF with a sensitivity 95% (95% CI, 83.08-99.39), specificity 74.14% (95% CI, 60.96-84.74), positive predictive value 71.70% (95% CI, 61.96-79.75), negative predictive value 95.56% (95% CI, 84.67-98.82) and accuracy 82.65% (95% CI, 73.69-89.56). In addition, MMP-9 showed a significant negative correlation with ejection fraction and fractional shortening (P=0.01 and P=0.02, respectively). In conclusion; MMP-9 may be an independent sensitive marker with which to detect HF in children with RHD and it can predict the prognoses of these patients as it correlates with the severity of HF. Further studies considering MMP-9 in the detection of 'silent' RHD in school aged children and asymptomatic HF in children with known RHD especially in rural areas, are highly recommended.

Project description:BackgroundGuideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials.ObjectivesWe investigated predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use, and the associations between these medications and mortality/morbidity in a large real-world cohort with HFmrEF.Methods and resultsPatients with HFmrEF (EF 40-49%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality/HF hospitalization (HFH), and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF < 40%, while a negative control outcome analysis had cancer-related hospitalization as endpoint. Of 12 421 patients with HFmrEF, 84% received RASI/ARNI and 88% beta-blockers. Shared-independent predictors of RASI/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, and hypertension. In the matched cohorts, use of both RASI/ARNI and beta-blocker use was separately associated with lower risk of CV mortality/HFH [hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.83-0.98 and HR = 0.82, 95% CI: 0.74-0.90, respectively] and of all-cause mortality (HR = 0.75, 95% CI: 0.69-0.81 and HR = 0.79, 95% CI: 0.72-0.87, respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome.ConclusionsRASI/ARNI and beta-blockers were extensively used in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm the real-world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.

Dataset Information

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure.

Publications

Matrix Metalloproteinase 2 as a Pharmacological Target in Heart Failure.

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