Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is Associated With Right Ventricular Dysfunction and Nitrative Stress in Heart FailureCLINICAL.

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Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is Associated With Right Ventricular Dysfunction and Nitrative Stress in Heart FailureCLINICAL PERSPECTIVE by David J. Kennedy, Kevin Shrestha, Brendan Sheehey, Xinmin S. Li, Anuradha Guggilam, Yuping Wu, Michael Finucan, Alaa Gabi, Charles M. Medert, Kristen Westfall, Allen Borowski, Olga Fedorova, Alexei Y. Bagrov, and W.H. Wilson Tang Circ Heart Fail Volume 8(6):1068-1076 November 17, 2015 Copyright © American Heart Association, Inc. All rights reserved.

Marinobufagenin levels in heart failure. Marinobufagenin levels in heart failure. Comparison of plasma marinobufagenin levels between non–heart failure (HF) participants and HF participants with reduced (≤40) or preserved (>40) left ventricular ejection fraction (EF). **P<0.001 vs control, by Student’s t test with Bonferroni’s correction. David J. Kennedy et al. Circ Heart Fail. 2015;8:1068-1076 Copyright © American Heart Association, Inc. All rights reserved.

Kaplan–Meier analysis of major adverse cardiac events (MACE) in participants with heart failure. Kaplan–Meier analysis of major adverse cardiac events (MACE) in participants with heart failure. A, Patients with heart failure (n=245) stratified according to optimal cutoff for plasma marinobufagenin (MBG) as follows: Low MBG (<574 pmol/L) or High MBG (≥574 pmol/L). B, Subgroup analysis of patients with heart failure (n=115) with serial blood draws from admission to predischarge at 48 to 72 hours stratified according to optimal cutoff for change in plasma MBG as follows: decreasing MBG (<5%) or increasing MBG (≥5%). David J. Kennedy et al. Circ Heart Fail. 2015;8:1068-1076 Copyright © American Heart Association, Inc. All rights reserved.

Elevated marinobufagenin (MBG) levels contribute to nitrative stress. Elevated marinobufagenin (MBG) levels contribute to nitrative stress. Echocardiographic measures of cardiac ejection fraction (A) and diastolic left ventricular internal dimension (LVIDd; B) after 4 weeks of either left anterior descending (LAD) ligation (LADx) or MBG infusion. Gene expression of calcium-handling proteins sarcoplasmic reticulum calcium ATPase (SERCA2a; C) and sodium calcium exchanger (NCX-1; D), and hypertrophic markers beta myosin heavy chain (βMHC; E) and atrial natriuretic peptide (ANP; F) after 4 weeks of LADx. Plasma MBG (G) levels are increased 4 weeks after LAD ligation in a post–myocardial infarction heart failure model. H, Adrenal tissue MBG levels 1 week after LAD ligation. P values were calculated using the Mann–Whitney U test. David J. Kennedy et al. Circ Heart Fail. 2015;8:1068-1076 Copyright © American Heart Association, Inc. All rights reserved.

Elevated marinobufagenin (MBG) levels contribute to nitrative stress. Elevated marinobufagenin (MBG) levels contribute to nitrative stress. After 4 week infusion of MBG, plasma levels of MBG (A) and myeloperoxidase (MPO; B), as well as methylated arginine metabolites asymmetrical dimethylarginine (ADMA, C), symmetrical dimethylarginine (SDMA, D), and monomethyl arginine (MMA, E), are increased vs vehicle-treated mice. P values were calculated using the Mann–Whitney U test. David J. Kennedy et al. Circ Heart Fail. 2015;8:1068-1076 Copyright © American Heart Association, Inc. All rights reserved.

Elevated marinobufagenin (MBG) levels contribute to fibrosis. Elevated marinobufagenin (MBG) levels contribute to fibrosis. Representative picosirius red histology (A) and quantitative morphometry (B) from mouse hearts after 4 week MBG infusion. Scale bar represents 100 μm. P values were calculated using the Mann–Whitney U test. David J. Kennedy et al. Circ Heart Fail. 2015;8:1068-1076 Copyright © American Heart Association, Inc. All rights reserved.