Proteomic Analysis of Effects of Spironolactone in Heart Failure With Preserved Ejection Fraction
| Autor: | Ali Javaheri, Ahmed Diab, Lei Zhao, Chenao Qian, Jordana B. Cohen, Payman Zamani, Anupam Kumar, Zhaoqing Wang, Christina Ebert, Joseph Maranville, Erika Kvikstad, Michael Basso, Vanessa van Empel, A. Mark Richards, Robert N. Doughty, Ernst Rietzschel, Karl Kammerhoff, Joseph Gogain, Peter Schafer, Dietmar A. Seiffert, David A. Gordon, Francisco Ramirez-Valle, Douglas L. Mann, Thomas P. Cappola, Julio A. Chirinos |
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| Přispěvatelé: | Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Proteomics
Caspases/pharmacology Proteome Insulins Phospholipid Transfer Proteins/pharmacology Spironolactone Apelin/pharmacology Mineralocorticoid Receptor Antagonists/therapeutic use Humans Phospholipid Transfer Proteins Mineralocorticoid Receptor Antagonists Liver X Receptors Heart Failure Biological Products Biological Products/pharmacology Stroke Volume Spironolactone/adverse effects Caspase Insulins/therapeutic use Treatment Outcome Stroke Volume/physiology Caspases Apelin Americas Glycoprotein Cardiology and Cardiovascular Medicine |
| Zdroj: | Circulation-Heart Failure, 15(9):e009693, 827-837. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 1941-3289 |
| Popis: | Background: The TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) suggested clinical benefits of spironolactone treatment among patients with heart failure with preserved ejection fraction enrolled in the Americas. However, a comprehensive assessment of biologic pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction has not been performed. Methods: We conducted aptamer-based proteomic analysis utilizing 5284 modified aptamers to 4928 unique proteins on plasma samples from TOPCAT participants from the Americas (n=164 subjects with paired samples at baseline and 1 year) to identify proteins and pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction. Mean percentage change from baseline was calculated for each protein. Additionally, we conducted pathway analysis of proteins altered by spironolactone. Results: Spironolactone therapy was associated with proteome-wide significant changes in 7 proteins. Among these, CARD18 (caspase recruitment domain-containing protein 18), PKD2 (polycystin 2), and PSG2 (pregnancy-specific glycoprotein 2) were upregulated, whereas HGF (hepatic growth factor), PLTP (phospholipid transfer protein), IGF2R (insulin growth factor 2 receptor), and SWP70 (switch-associated protein 70) were downregulated. CARD18, a caspase-1 inhibitor, was the most upregulated protein by spironolactone (−0.5% with placebo versus +66.5% with spironolactone, P Conclusions: Proteomic analysis in the TOPCAT trial revealed proteins and pathways altered by spironolactone, including the caspase inhibitor CARD18 and multiple pathways that involved collagens. In addition to effects on fibrosis, our studies suggest potential antiapoptotic effects of spironolactone in heart failure with preserved ejection fraction, a hypothesis that merits further exploration. |
| Databáze: | OpenAIRE |
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