What question did this study set out to answer?

To examine myocardial matrix metalloproteinase (MMP-2 and MMP-9) levels in ischemic and idiopathic end-stage heart failure and assess direct enzymatic inhibition by ACE inhibitors.

October 15, 2002HeartOpen Access

Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP

Q: What is the clinical evidence from this study?

Study design: Case-Control. Population: Heart failure (n=35). Intervention: Heart failure (ischaemic and idiopathic dilated cardiomyopathy) vs. Controls. Primary outcome: Active matrix metalloproteinases (MMP-2 and MMP-9) levels in myocardium.

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Key result

ACE inhibitors directly inhibit active MMP-9 in vitro, which is elevated ~3-fold in heart failure.

n=35

Population

Myocardium samples from patients with end-stage heart failure due to coronary artery disease or idiopathic…

Comparison

In vitro application of ACE inhibitors. vs Myocardium from controls and uninhibited state.

Design

Preclinical

Authors

DRDirk ReinhardtGoethe University Frankfurt

Discussion

Member takes

Overview

ACE inhibitors may directly inhibit MMP-9 in failing hearts; hypothesis-generating and should not yet change practice.

Key Points

To examine myocardial matrix metalloproteinase (MMP-2 and MMP-9) levels in ischemic and idiopathic end-stage heart failure and assess direct enzymatic inhibition by ACE inhibitors.
Extracted myocardial tissue samples from explanted hearts of patients with coronary artery disease (n = 13), idiopathic dilated cardiomyopathy (n = 16), and non-failing controls (n = 6).
Quantified active MMP-2 and MMP-9 using ELISA, determined gelatinolytic activity via zymography, and measured gene expression using reverse transcriptase polymerase chain reaction.
Assayed in vitro inhibitory concentration (IC50) values for captopril, ramiprilate, and lisinopril against MMP-2 and MMP-9, testing sensitivity to zinc excess.
Active MMP-9 was significantly elevated in coronary artery disease (mean [SD] 1.6 [0.35] ng/ml) and dilated cardiomyopathy (2.11 [0.54] ng/ml) compared to controls (0.53 [0.15] ng/ml), while MMP-2 was elevated only in dilated cardiomyopathy (3.68 [0.41] ng/ml), with no corresponding upregulation of mRNA expression.
Captopril and ramiprilate inhibited in vitro activity of both MMP-2 (IC50: 2.0 [0.16] and 2.1 [0.3] mmol/l) and MMP-9 (IC50: 1.65 [0.18] and 2.0 [0.3] mmol/l), whereas lisinopril inhibited MMP-9 (IC50: 7.86 [2.23] mmol/l) but not MMP-2 (IC50: 7.4 [0.88] mmol/l), with all inhibition blunted by zinc.

Study Design

Type

Case-Control (n=35)

Structured PICO

Population

35 subjects, comprising 29 patients with heart failure (coronary artery disease or idiopathic dilated cardiomyopathy) and 6 controls.

Exposure

In vitro application of ACE inhibitors (captopril, ramiprilate, lisinopril).

Comparator

Myocardium from controls (for tissue analysis) and uninhibited state (for in vitro analysis).

Outcome

Active form of MMP-2 and MMP-9, MMP activity, and mRNA expression of MMPs.surrogate

MMP-9 activity is upregulated in failing myocardium regardless of etiology, and ACE inhibitors may exert direct inhibitory effects on MMP activity independent of their systemic effects.

Cite This Study

Dirk Reinhardt (2002) conducted a case-control in Heart failure (n=35). Heart failure (ischaemic and idiopathic dilated cardiomyopathy) vs. Controls was evaluated on Active matrix metalloproteinases (MMP-2 and MMP-9) levels in myocardium. Active MMP-9 was increased in heart failure versus controls (1.6 and 2.11 vs 0.53 ng/ml), and ACE inhibitors directly inhibited MMP activity in vitro.

synapsesocial.com/papers/6aa144bbb78df6d0beed6b96 https://doi.org/10.1136/heart.88.5.525

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October 15, 2002HeartOpen Access

Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP

View Full Paper

Ask AI

Bookmark

Key result

ACE inhibitors directly inhibit active MMP-9 in vitro, which is elevated ~3-fold in heart failure.

n=35

Population

Myocardium samples from patients with end-stage heart failure due to coronary artery disease or idiopathic…

Comparison

In vitro application of ACE inhibitors. vs Myocardium from controls and uninhibited state.

Design

Preclinical

Authors

DRDirk ReinhardtGoethe University Frankfurt

Discussion

Member takes

Overview

ACE inhibitors may directly inhibit MMP-9 in failing hearts; hypothesis-generating and should not yet change practice.

Key Points

To examine myocardial matrix metalloproteinase (MMP-2 and MMP-9) levels in ischemic and idiopathic end-stage heart failure and assess direct enzymatic inhibition by ACE inhibitors.
Extracted myocardial tissue samples from explanted hearts of patients with coronary artery disease (n = 13), idiopathic dilated cardiomyopathy (n = 16), and non-failing controls (n = 6).
Quantified active MMP-2 and MMP-9 using ELISA, determined gelatinolytic activity via zymography, and measured gene expression using reverse transcriptase polymerase chain reaction.
Assayed in vitro inhibitory concentration (IC50) values for captopril, ramiprilate, and lisinopril against MMP-2 and MMP-9, testing sensitivity to zinc excess.
Active MMP-9 was significantly elevated in coronary artery disease (mean [SD] 1.6 [0.35] ng/ml) and dilated cardiomyopathy (2.11 [0.54] ng/ml) compared to controls (0.53 [0.15] ng/ml), while MMP-2 was elevated only in dilated cardiomyopathy (3.68 [0.41] ng/ml), with no corresponding upregulation of mRNA expression.
Captopril and ramiprilate inhibited in vitro activity of both MMP-2 (IC50: 2.0 [0.16] and 2.1 [0.3] mmol/l) and MMP-9 (IC50: 1.65 [0.18] and 2.0 [0.3] mmol/l), whereas lisinopril inhibited MMP-9 (IC50: 7.86 [2.23] mmol/l) but not MMP-2 (IC50: 7.4 [0.88] mmol/l), with all inhibition blunted by zinc.

Study Design

Type

Case-Control (n=35)

Structured PICO

Population

35 subjects, comprising 29 patients with heart failure (coronary artery disease or idiopathic dilated cardiomyopathy) and 6 controls.

Exposure

In vitro application of ACE inhibitors (captopril, ramiprilate, lisinopril).

Comparator

Myocardium from controls (for tissue analysis) and uninhibited state (for in vitro analysis).

Outcome

Active form of MMP-2 and MMP-9, MMP activity, and mRNA expression of MMPs.surrogate

MMP-9 activity is upregulated in failing myocardium regardless of etiology, and ACE inhibitors may exert direct inhibitory effects on MMP activity independent of their systemic effects.

Cite This Study

synapsesocial.com/papers/6aa144bbb78df6d0beed6b96 https://doi.org/10.1136/heart.88.5.525

Also Consider

Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context:

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