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Cathepsin A inhibition attenuates myocardial infarction-induced heart failure on the functional and proteomic levels.
- Source :
- Journal of Translational Medicine; 5/31/2016, Vol. 14, p1-11, 11p
- Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>Myocardial infarction (MI) is a major cause of heart failure. The carboxypeptidase cathepsin A is a novel target in the treatment of cardiac failure. We aim to show that recently developed inhibitors of the protease cathepsin A attenuate post-MI heart failure.<bold>Methods: </bold>Mice were subjected to permanent left anterior descending artery (LAD) ligation or sham operation. 24 h post-surgery, LAD-ligated animals were treated with daily doses of the cathepsin A inhibitor SAR1 or placebo. After 4 weeks, the three groups (sham, MI-placebo, MI-SAR1) were evaluated.<bold>Results: </bold>Compared to sham-operated animals, placebo-treated mice showed significantly impaired cardiac function and increased plasma BNP levels. Cathepsin A inhibition prevented the increase of plasma BNP levels and displayed a trend towards improved cardiac functionality. Proteomic profiling was performed for the three groups (sham, MI-placebo, MI-SAR1). More than 100 proteins were significantly altered in placebo-treated LAD ligation compared to the sham operation, including known markers of cardiac failure as well as extracellular/matricellular proteins. This ensemble constitutes a proteome fingerprint of myocardial infarction induced by LAD ligation in mice. Cathepsin A inhibitor treatment normalized the marked increase of the muscle stress marker CA3 as well as of Igγ 2b and fatty acid synthase. For numerous further proteins, cathepsin A inhibition partially dampened the LAD ligation-induced proteome alterations.<bold>Conclusions: </bold>Our proteomic and functional data suggest that cathepsin A inhibition has cardioprotective properties and support a beneficial effect of cathepsin A inhibition in the treatment of heart failure after myocardial infarction. [ABSTRACT FROM AUTHOR]
- Subjects :
- MYOCARDIAL infarction
HEART failure
CARBOXYPEPTIDASES
ARTERIES
CATHEPSINS
MYOCARDIAL infarction complications
THERAPEUTIC use of protease inhibitors
ANIMAL experimentation
ANIMALS
ANTHROPOMETRY
BIOLOGICAL models
CELL lines
HEART ventricles
LIGATURE (Surgery)
MICE
PAPER chromatography
PEPTIDES
PROTEOLYTIC enzymes
RATS
PROTEOMICS
PROTEASE inhibitors
CHEMICAL inhibitors
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 14
- Database :
- Complementary Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 115880718
- Full Text :
- https://doi.org/10.1186/s12967-016-0907-8