What question did this study set out to answer?

To determine whether matrix metalloproteinases and tissue inhibitors of metalloproteinases are differentially regulated in the myocardium of failing human hearts.

October 27, 1998CirculationOpen Access

Differential Expression of Tissue Inhibitors of Metalloproteinases in the Failing Human Heart

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Ischemic and idiopathic dilated cardiomyopathy (n=46). Primary outcome: Cardiac expression of TIMP-1 to -4 and MMP-9 transcripts and proteins, and total gelatinolytic activity.

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Key result

Failing human hearts exhibited significant downregulation of TIMP-1 and -3 and upregulation of MMP-9 and gelatinolytic activity compared to nonfailing controls.

Authors

YLYun You LiThe Ohio State University Wexner Medical Center AFArthur M. FeldmanThe Wistar Institute YSYi SunTata Institute of Fundamental Research

Discussion

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Implication

Observed MMP/TIMP imbalance in failing hearts is hypothesis-generating; leaves open therapeutic targeting in HF.

Key Points

To determine whether matrix metalloproteinases and tissue inhibitors of metalloproteinases are differentially regulated in the myocardium of failing human hearts.
Analyzed left ventricular tissue samples from patients with ischemic cardiomyopathy (ICM, n=16), idiopathic dilated cardiomyopathy (DCM, n=15), and nonfailing control hearts (n=15).
Measured mRNA transcript and protein levels of TIMP-1 through TIMP-4 and MMP-9 using Northern blot, ELISA, Western blot, and gelatin zymography.
TIMP-1 and TIMP-3 mRNA transcripts and protein levels were significantly downregulated in both ICM and DCM myocardium compared to nonfailing controls.
TIMP-4 protein was selectively reduced in ICM myocardium, while MMP-9 protein abundance and total gelatinolytic activity were significantly upregulated across failing hearts.

Study Design

Type

Observational (n=46)

PICO

Population

Ischemic and idiopathic dilated cardiomyopathy (n=46)

Primary Outcome

Cardiac expression of TIMP-1 to -4 and MMP-9 transcripts and proteins, and total gelatinolytic activity

Cite This Study

Li et al. (1998) conducted an observational in Ischemic and idiopathic dilated cardiomyopathy (n=46). Failing human hearts exhibited significant downregulation of TIMP-1 and -3 and upregulation of MMP-9 and gelatinolytic activity compared to nonfailing controls.

synapsesocial.com/papers/6a0f141c25c30b2cc7fa171e https://doi.org/10.1161/01.cir.98.17.1728

Topics

Heart failure HFrEF treatment

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Differential Expression of Tissue Inhibitors of Metalloproteinases in the Failing Human Heart

Discussion

Member takes

Implication

Key Points

Study Design

PICO

Cite This Study

Topics

Differential Expression of Tissue Inhibitors of Metalloproteinases in the Failing Human Heart

Discussion

Member takes

Implication

Key Points

Study Design

PICO

Cite This Study

Also Consider

Topics

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