A Quantitative Gene Expression Profile of Matrix Metalloproteinases (MMPS) and Their Inhibitors (TIMPS) in the Myocardium of Patients With Deteriorating Heart Failure Requiring Left Ventricular Assist Device Support
Abstract
Background Mechanisms underlying the rapid deterioration of heart failure patients who subsequently require left ventricular assist device (LVAD) support are poorly understood. Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play a key role in myocardial remodelling and heart failure. We hypothesized that MMP and TIMP expression would be altered in these patients.Methods Quantitative polymerase chain reaction was used to measure myocardial messenger RNA levels of MMP1 to MMP14, TIMP1 to TIMP4, collagen I and collagen III in 24 dilated cardiomyopathy (DCM) patients with deteriorating clinical status who required LVAD support (LVAD Group) and in 7 stable DCM patients undergoing transplantation without need for LVAD support (Tx Group).Results Levels of MMP1, MMP8 and TIMP4 were higher in the LVAD Group compared with the Tx Group (188% +/- 141%, 646% +/- 432%, and 66% +/- 33% higher, respectively, p < 0.05) whereas MMP2, MMP9, MMP10, MMP11, and MMP14 levels were similar. MMP3, MMP7, MMP12, and MMP13 were undetectable. All TIMPs were generally higher in the LVAD group, but only TIMP4 reached significance. Collagen I and III were not altered. We tested for correlations between MMP and TIMP expression with myocardial cytokine levels. MMP8 correlated positively with interleukin-6 and interleukin-1beta, suggesting a link between cytokines and MMPs in these patients.Conclusions The data show that high myocardial collagenase (MMP1 and MMP8) expression without compensatory changes in collagen or TIMP expression is a feature of patients requiring LVAD support. This may be linked in part to elevated cytokine expression and suggests collagenase activity may be an important therapeutic target in deteriorating heart failure.
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Regulation of myocardial ECM by adipokines is of great importance in obesity.
“With respect to obesity, it is important to consider the concept that regulation of myocardial ECM by adipokines is of great importance (77, 99).”
From Cardiac remodeling in obesity (2008) · cites this paper as [99]
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- Authors
- Felkin, L. E., Birks, E. J., George, R., Wong, S., Khaghani, A., Yacoub, M. H., & Barton, P. J. R.
- Affiliations
- Imperial College London (GB)
- Royal Brompton & Harefield NHS Foundation Trust (GB)
- Corresponding author
- Barton, Paul J.R.
- Venue
- The Journal of Heart and Lung Transplantation
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 25
- Issue
- 12
- Pages
- 1413-1419
- ISSN
- 1053-2498 (ISSN-L)
- OpenAlex
- W2028237696
- Cited by
- 59
- References
- 26
- Citations by year
- 2023: 2 · 2022: 1 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 5 · 2012: 2
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Heart and Lung Transplantation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Mechanical Circulatory Support Devices
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- matrix metalloproteinases, tissue inhibitors of metalloproteinases, heart failure decompensation, left ventricular assist device, dilated cardiomyopathy, myocardial remodelling, MMP-8, MMP-1, TIMP-4, type I collagen, type III collagen, interleukin-6, IL-1β, heart transplantation
- MeSH terms
- Tissue Inhibitor of Metalloproteinase-4, Adolescent, Adult, Cardiac Output, Low, Child, Female, Heart Ventricles, Heart-Assist Devices, Humans, Male, Middle Aged, Myocardium, Severity of Illness Index, Disease Progression, Tissue Inhibitor of Metalloproteinases, Matrix Metalloproteinase 1, Matrix Metalloproteinases, Matrix Metalloproteinase 8, Gene Expression Profiling
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