Mitochondrial Integrity and Function in the Progression of Early Pressure Overload–Induced Left Ventricular Remodeling by Antoine H. Chaanine, K Sreekumaran.

Slides:

Advertisements

Similar presentations

Date of download: 5/27/2016 Copyright © The American College of Cardiology. All rights reserved. From: Increased myocardial apoptosis in patients with.

Advertisements

Date of download: 5/28/2016 Copyright © The American College of Cardiology. All rights reserved. From: Contractile Function During Angiotensin-II Activation:

Date of download: 6/1/2016 Copyright © The American College of Cardiology. All rights reserved. From: Induction and reversal of cardiac phenotype of human.

Date of download: 6/9/2016 Copyright © The American College of Cardiology. All rights reserved. From: Cardiomyocyte-Specific Deletion of Gsk3α Mitigates.

Date of download: 6/23/2016 Copyright © The American College of Cardiology. All rights reserved. From: 17-Beta-Estradiol increases cardiac remodeling and.

Date of download: 6/25/2016 Copyright © The American College of Cardiology. All rights reserved. From: Effect of ATP-Sensitive Potassium Channel Agonists.

Date of download: 7/7/2016 Copyright © The American College of Cardiology. All rights reserved. From: Acute Phosphodiesterase 5 Inhibition Mimics Hemodynamic.

Date of download: 9/17/2016 Copyright © The American College of Cardiology. All rights reserved. From: Angiotensin II type 1 receptor antagonist decreases.

Date of download: 9/19/2016 Copyright © The American College of Cardiology. All rights reserved. From: Exenatide Reduces Infarct Size and Improves Cardiac.

Cardiac effects of acute exhaustive exercise in a rat model

Volume 78, Issue 11, Pages (December 2010)

Increased Apoptosis, Altered Oxygen Signaling, and Antioxidant Defenses in First- Trimester Pregnancies with High-Resistance Uterine Artery Blood Flow

Journal of Molecular and Cellular Cardiology

Molecular Therapy - Nucleic Acids

Molecular and Functional Alterations in a Mouse Cardiac Model of Friedreich Ataxia Michael Li-Hsuan Huang, Sutharshani Sivagurunathan, Samantha Ting,

In Vivo Cardiac Cellular Reprogramming Efficacy Is Enhanced by Angiogenic Preconditioning of the Infarcted Myocardium With Vascular Endothelial Growth.

Targeting DNA Replication before it Starts

Choline Diet and Its Gut Microbe–Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload–Induced Heart FailureCLINICAL PERSPECTIVE by.

Dapper-1 Induces Myocardial Remodeling Through Activation of Canonical Wnt Signaling in CardiomyocytesNovelty and Significance by Marco Hagenmueller, Johannes.

Mitogen‐Activated Protein Kinase and Intracellular Polyamine Signaling Is Involved in TRPV1 Activation–Induced Cardiac Hypertrophy by Mai Chen, Jiajia.

Statins Alter Smooth Muscle Cell Accumulation and Collagen Content in Established Atheroma of Watanabe Heritable Hyperlipidemic Rabbits by Yoshihiro Fukumoto,

Transforming Growth Factor‐β Receptor III is a Potential Regulator of Ischemia‐Induced Cardiomyocyte Apoptosis by Fei Sun, Xin Li, Wen‐Qi Duan, Wei Tian,

Passive Ventricular Constraint Prevents Transmural Shear Strain Progression in Left Ventricle Remodeling by Allen Cheng, Tom C. Nguyen, Marcin Malinowski,

Activation of Liver-X-Receptor α But Not Liver-X-Receptor β Protects Against Myocardial Ischemia/Reperfusion InjuryCLINICAL PERSPECTIVE by Qing He, Jun.

Targeted Disruption of the Lama3 Gene in Adult Mice Is Sufficient to Induce Skin Inflammation and Fibrosis Monika Pesch, Sabrina König, Monique Aumailley

Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis

Volume 99, Issue 3, Pages (October 1999)

Electron transport chain dysfunction in neonatal pressure-overload hypertrophy precedes cardiomyocyte apoptosis independent of oxidative stress Eric.

Inhibition of ILK by QLT-0267 suppresses type I and type III collagen expression and ameliorates interstitial collagen deposition and renal fibrosis after.

Masanobu Ishii et al. BTS 2017;2:

Cardiac effects of acute exhaustive exercise in a rat model

Cell-based gene therapy modifies matrix remodeling after a myocardial infarction in tissue inhibitor of matrix metalloproteinase-3–deficient mice Denis.

Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure.

Brian P. Shapiro, MD, Horng H. Chen, MD, John C

Diabetic hearts have lower basal urocortin levels that fail to increase after cardioplegic arrest: Association with increased apoptosis and postsurgical.

Association of smooth muscle cell phenotypes with extracellular matrix disorders in thoracic aortic dissection Lixin Wang, MD, PhD, Jing Zhang, MD, PhD,

Controlled release of ascorbic acid from gelatin hydrogel attenuates abdominal aortic aneurysm formation in rat experimental abdominal aortic aneurysm.

Fig. 3. Obese IFN-γ−/− mice develop accelerated NAFLD with fibrosis.

Michael G. Katz, MD, PhD, Elizabeth Brandon-Warner, PhD, Anthony S

Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft Mitsuteru Handa, MD, Wei Li,

Depletion of primary cilia in articular chondrocytes results in reduced Gli3 repressor to activator ratio, increased Hedgehog signaling, and symptoms.

Nathalie Roy, MD, Ingeborg Friehs, MD, Douglas B

The effect of matrix metalloproteinase 2 and matrix metalloproteinase 2/9 deletion in experimental post-thrombotic vein wall remodeling Kristopher B.

Volume 67, Issue 1, Pages (January 2005)

Volume 25, Issue 11, Pages (November 2017)

Daniel J. Wong, MD, Daniel Y. Lu, MD, Clinton D

Induction of human aortic myofibroblast-mediated extracellular matrix dysregulation: A potential mechanism of fluoroquinolone-associated aortopathy David.

MI during active phase (ZT13) leads to infarct expansion and reduced cardiac function MI during active phase (ZT13) leads to infarct expansion and reduced.

Volume 85, Issue 1, Pages (January 2014)

Lukas J. Motloch et al. BTS 2017;2:

Left Ventricular Fibrosis and Systolic Hypertension Persist in a Repaired Aortic Coarctation Model Jie Liu, PhD, Douglas Drak, BSc, Anish Krishnan, BSc,

Volume 87, Issue 1, Pages (January 2015)

Marinus A. Borgdorff, Beatrijs Bartelds, Michael G

Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft Mitsuteru Handa, MD, Wei Li,

Safety and efficacy of high-dose adeno-associated virus 9 encoding sarcoplasmic reticulum Ca2+ adenosine triphosphatase delivered by molecular cardiac.

Myocyte apoptosis occurs early during the development of pressure-overload hypertrophy in infant myocardium Yeong-Hoon Choi, MD, Douglas B. Cowan, PhD,

Induction of heart failure by minimally invasive aortic constriction in mice: Reduced peroxisome proliferator-activated receptor γ coactivator levels.

Volume 78, Issue 11, Pages (December 2010)

Impaired ECM protein synthesis in infarcted area of S100a4cre+/− × Fstl1flox/flox mice Impaired ECM protein synthesis in infarcted area of S100a4cre+/−

Volume 14, Issue 1, Pages (July 2011)

Hironori Hara et al. BTS 2018;3:

Ioannis Smyrnias et al. JACC 2019;73:

Anish Krishnan, BSc, Douglas Drak, BSc, Shisan Bao, PhD, David S

Volume 128, Issue 1, Pages (January 2005)

Early and persistent activation of myocardial apoptosis, bax and caspases: insights into mechanisms of progression of heart failure Gordon W Moe, George.

Deep vein thrombosis resolution is impaired in diet-induced type 2 diabetic mice Fatiha Bouzeghrane, PhD, Xiaochun Zhang, MD, BSc, Guylaine Gevry, BSc,

Expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP in serosal tissue of intraperitoneal organs and adhesions Nasser Chegini,

Effect of M-cadherin RNAi on apoptosis in confluent C2C12 myoblasts.

miR-25 Tough Decoy Enhances Cardiac Function in Heart Failure

Volume 85, Issue 1, Pages (January 2014)

Presentation transcript:

Mitochondrial Integrity and Function in the Progression of Early Pressure Overload–Induced Left Ventricular Remodeling by Antoine H. Chaanine, K Sreekumaran Nair, Robert H. Bergen, Katherine Klaus, Adam J. Guenzel, Roger J. Hajjar, and Margaret M. Redfield J Am Heart Assoc Volume 6(6):e005869 June 15, 2017 © 2017 Antoine H. Chaanine et al.

Serial assessment of LV volumes at 3 and 8 weeks post‐ascending aortic banding (AAB) in the different phenotypes. Serial assessment of LV volumes at 3 and 8 weeks post‐ascending aortic banding (AAB) in the different phenotypes. LV end‐diastolic (LVEDV) and LV end‐systolic (LVESV) volume at 3 (A and B) and 8 (C and D) weeks post‐AAB. Individual data points, box and whisker plots showing the median, interquartile range, and maximum and minimum values. *P<0.05 vs sham; +P<0.05 vs CR and ‡P<0.05 vs MILD. CR indicates concentric remodeling; MILD, mild eccentric remodeling; MOD, moderate eccentric remodeling. Antoine H. Chaanine et al. J Am Heart Assoc 2017;6:e005869 © 2017 Antoine H. Chaanine et al.

Echocardiographic assessment of the different phenotypes. Echocardiographic assessment of the different phenotypes. A, Representative M‐mode images at the level of the midpapillary muscle in the different phenotypes. B and C, LV septal (IVSd) and posterior wall (LVPWd) thickness across the different phenotypes. D, LV ejection fraction (LVEF) across the different phenotypes. Individual data points, box and whisker plots showing the median, interquartile range, and maximum and minimum values. *P<0.05 vs sham; +P<0.05 vs CR and ‡P<0.05 vs MILD. CR indicates concentric remodeling; IVSd, interventricular septal thickness in end‐diastole; LVEF, left ventricular ejection fraction; LVPWd, left ventricular wall thickness in end‐diastole; MILD, mild eccentric remodeling; MOD, moderate eccentric remodeling. Antoine H. Chaanine et al. J Am Heart Assoc 2017;6:e005869 © 2017 Antoine H. Chaanine et al.

Hemodynamic assessment of the different phenotypes. Hemodynamic assessment of the different phenotypes. A, Top panel: Representative P–V loop tracings at steady state (left) and with inferior vena cava constriction (right) in the different phenotypes. Bottom panel: Representative P–V loop tracings scaled for diastolic pressures at steady state (left) and with inferior vena cava constriction (right) in the different phenotypes. LV maximum pressure (LVPmax) (B), LV end‐diastolic pressure (LVEDP) (C), the dimensionless chamber stiffness index (DCSI) (D) and end‐systolic elastance (Ees) (E) across the different phenotypes. Individual data points, box and whisker plots showing the median, interquartile range, and maximum and minimum values. *P<0.05 vs sham; +P<0.05 vs CR and ‡P<0.05 vs MILD. CR indicates concentric remodeling; LV, left ventricular; MILD, mild eccentric remodeling; MOD, moderate eccentric remodeling; P–V, pressure–volume. Antoine H. Chaanine et al. J Am Heart Assoc 2017;6:e005869 © 2017 Antoine H. Chaanine et al.

LV interstitial fibrosis, markers of pathological hypertrophy and fetal gene expression in the different phenotypes. LV interstitial fibrosis, markers of pathological hypertrophy and fetal gene expression in the different phenotypes. A, Representative photomicrographs of LV tissue stained with Picrosirius red taken by light (upper and bottom row) and polarized microscopy (middle row). Upper and middle row scale bar 200 μm. Bottom row scale bar 100 μm. B, Interstitial fibrosis assessed by collagen area fraction (CAF). C and D, Collagen I and III mRNA expression relative to sham. E, F, and G, Alpha‐skeletal muscle actin (ACTA1), Beta‐myosin heavy chain (β‐MyHC) and brain natriuretic peptide (BNP) mRNA expression relative to sham. Individual data points, box and whisker plots showing the median, interquartile range, and maximum and minimum values. *P<0.05 vs sham; +P<0.05 vs CR and ‡P<0.05 vs MILD. CR indicates concentric remodeling; MILD, mild eccentric remodeling; MOD, moderate eccentric remodeling. Antoine H. Chaanine et al. J Am Heart Assoc 2017;6:e005869 © 2017 Antoine H. Chaanine et al.

Assessment of the matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) in the different phenotypes. Assessment of the matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) in the different phenotypes. A, MMP‐2, MMP‐9, TIMP‐1, and TIMP‐2 expression in the different phenotypes compared to sham. Blue arrows showing MMP‐2 monomer and dimer at 75 and 150 kDa, respectively. B, Ratios of MMP‐2 and MMP‐9 over TIMP‐1 and TIMP‐2, respectively. The n number of animals studied for immunoblotting in the sham, CR, MILD, and MOD groups is 5, 8, 8, and 6, respectively. Bar graphs show mean and SD. *P<0.05 vs sham; +P<0.05 vs CR and ‡P<0.05 vs MILD. CR indicates concentric remodeling; MILD, mild eccentric remodeling; MOD, moderate eccentric remodeling. Antoine H. Chaanine et al. J Am Heart Assoc 2017;6:e005869 © 2017 Antoine H. Chaanine et al.

Assessment of calcium cycling proteins, endoplasmic reticulum stress apoptotic and mitochondrial pro‐apoptotic markers, biogenesis, and content in the different phenotypes. Assessment of calcium cycling proteins, endoplasmic reticulum stress apoptotic and mitochondrial pro‐apoptotic markers, biogenesis, and content in the different phenotypes. A, SERCA2a and NCX‐1 expression and ratio of S16 phosphorylated to total phospholamban. B, CHOP expression. C, BNIP3 expression and Bax/Bcl‐2 ratio in the different phenotypes compared to sham. The n number of animals studied for immunoblotting in the sham, CR, MILD, and MOD groups is 5, 8, 8, and 6, respectively. Bar graphs show mean and SD. *P<0.05 vs sham; +P<0.05 vs CR and ‡P<0.05 vs MILD. CR indicates concentric remodeling; MILD, mild eccentric remodeling; MOD, moderate eccentric remodeling. Antoine H. Chaanine et al. J Am Heart Assoc 2017;6:e005869 © 2017 Antoine H. Chaanine et al.

Assessment of apoptosis in the different phenotypes. Assessment of apoptosis in the different phenotypes. A, TUNEL assay in the different phenotypes compared to sham. Images are 20× magnified, scale bar = 50 μm. The n number of studied animals for sham, CR, MILD, and MOD is 5, 8, 8, and 7, respectively. B, Cleaved caspase 3 relative to caspase 3 expression in the different phenotypes compared with sham. The n number of studied animals in the sham, CR, MILD, and MOD is 5, 8, 8, and 6, respectively. Bar graphs show mean and standard deviation. *P<0.05 vs sham; +P<0.05 vs CR and ‡P<0.05 vs MILD. CR indicates concentric remodeling; MILD, mild eccentric remodeling; MOD, moderate eccentric remodeling; TUNEL, terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labeling. Antoine H. Chaanine et al. J Am Heart Assoc 2017;6:e005869 © 2017 Antoine H. Chaanine et al.

Assessment of mitochondrial oxidative phosphorylation in the different phenotypes. Assessment of mitochondrial oxidative phosphorylation in the different phenotypes. A, Electron transport chain complexes I–V. B, Citrate synthase (CS) activity. C, COX IV activity. D, PGC‐1α expression. E, Mitochondrial to nuclear DNA ratio across the different phenotypes relative to sham. The n number of studied animals for sham, CR, MILD, and MOD is 5, 8, 8, and 6 for immunoblotting and 5, 8, 8, and 7 for CS and COX IV activity, respectively. Bar graphs show mean and SD. *P<0.05 vs sham; +P<0.05 vs CR and ‡P<0.05 vs MILD. CR indicates concentric remodeling; MILD, mild eccentric remodeling; MOD, moderate eccentric remodeling. Antoine H. Chaanine et al. J Am Heart Assoc 2017;6:e005869 © 2017 Antoine H. Chaanine et al.