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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 :
- Academic Search Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 115880718
- Full Text :
- https://doi.org/10.1186/s12967-016-0907-8