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Proteomic and Mechanistic Analysis of Spironolactone in Patients at Risk for HF
- Source :
- JACC: Heart Failure, JACC: Heart Failure, 2021, S2213-1779 (20), pp.30705-8. ⟨10.1016/j.jchf.2020.11.010⟩, JACC: Heart Failure, Elsevier/American College of Cardiology, 2021, S2213-1779 (20), pp.30705-8. ⟨10.1016/j.jchf.2020.11.010⟩, JACC-Heart Failure, 9(4), 268-277. ELSEVIER SCI LTD
- Publication Year :
- 2021
- Publisher :
- ELSEVIER SCI LTD, 2021.
-
Abstract
- OBJECTIVES This study sought to further understand the mechanisms underlying effect of spironolactone and assessed its impact on multiple plasma protein biomarkers and their respective underlying biologic pathways.BACKGROUND In addition to their beneficial effects in established heart failure (HF), mineralocorticoid receptor antagonists may act upstream on mechanisms, preventing incident HF. In people at risk for developing HF, the HOMAGE (Heart OMics in AGEing) trial showed that spironolactone treatment could provide antifibrotic and antiremodeling effects, potentially slowing the progression to HF.METHODS Baseline, 1-month, and 9-month (or last visit) plasma samples of HOMAGE participants were measured for protein biomarkers (n = 276) by using Olink Proseek-Multiplex cardiovascular and inflammation panels (Olink, Uppsala, Sweden). The effect of spironolactone on biomarkers was assessed by analysis of covariance and explored by knowledgebased network analysis. RESULTS A total of 527 participants were enrolled; 265 were randomized to spironolactone (25 to 50 mg/day) and 262 to standard care ("control"). The median (interquartile range) age was 73 years (69 to 79 years), and 26% were female. Spironolactone reduced biomarkers of collagen metabolism (e.g., COL1A1, MMP-2); brain natriuretic peptide; and biomarkers related to metabolic processes (e.g., PAPPA), inflammation, and thrombosis (e.g., IL17A, VEGF, and urokinase). Spironolactone increased biomarkers that reflect the blockade of the mineralocorticoid receptor (e.g., renin) and increased the levels of adipokines involved in the anti-inflammatory response (e.g., RARRES2) and biomarkers of hemostasis maintenance (e.g., tPA, UPAR), myelosuppressive activity (e.g., CCL16), insulin suppression (e.g., RETN), and inflammatory regulation (e.g., IL-12B).CONCLUSIONS Proteomic analyses suggest that spironolactone exerts pleiotropic effects including reduction in fibrosis, inflammation, thrombosis, congestion, and vascular function improvement, all of which may mediate cardiovascular protective effects, potentially slowing progression toward heart failure. (HOMAGE [Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure]; NCT02556450) (C) 2021 by the American College of Cardiology Foundation.
- Subjects :
- Male
Proteomics
[SDV]Life Sciences [q-bio]
Adipokine
Inflammation
030204 cardiovascular system & hematology
Pharmacology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Mineralocorticoid receptor
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Fibrosis
Renin–angiotensin system
Natriuretic Peptide, Brain
medicine
Humans
030212 general & internal medicine
Aged
Mineralocorticoid Receptor Antagonists
Heart Failure
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
business.industry
fibrosis
spironolactone
HEART-FAILURE INSIGHTS
medicine.disease
Brain natriuretic peptide
3. Good health
[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
CARDIAC MATRIX BIOMARKERS
[SDV] Life Sciences [q-bio]
renin-angiotensin-aldosterone system
chemistry
MYOCARDIAL-INFARCTION
inflammation
Heart failure
Spironolactone
SURVIVAL
EPLERENONE
Female
medicine.symptom
Cardiology and Cardiovascular Medicine
business
heart failure prevention
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Subjects
Details
- Language :
- English
- ISSN :
- 22131779
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- JACC-Heart Failure
- Accession number :
- edsair.doi.dedup.....ff2f9ef636912f7d1efd60c7c971fbe4