Comparative Proteome Profiling during Cardiac Hypertrophy and Myocardial Infarction Reveals Altered Glucose Oxidation by Differential Activation of Pyruvate Dehydrogenase E1 Component Subunit β

2015 ◽  
Vol 427 (11) ◽  
pp. 2104-2120 ◽  
Author(s):  
Arkadeep Mitra ◽  
Trayambak Basak ◽  
Shadab Ahmad ◽  
Kaberi Datta ◽  
Ritwik Datta ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Pyruvate Dehydrogenase ◽  
Glucose Oxidation ◽  
Differential Activation ◽  
Proteome Profiling ◽  
Altered Glucose

Altered K+ current of ventricular myocytes in rats with chronic myocardial infarction

1998 ◽  
Vol 274 (1) ◽  
pp. H259-H265 ◽  
Author(s):  
George J. Rozanski ◽  
Zhi Xu ◽  
Kun Zhang ◽  
Kaushik P. Patel
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Pyruvate Dehydrogenase ◽  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Heart Weight ◽  
Transient Outward Current ◽  
Coronary Artery Ligation ◽  
Channel Function ◽  
Failing Heart

The aim of the present study was to define the cellular mechanisms underlying changes in K+ channel function in the failing heart after myocardial infarction. Rats with left coronary artery ligation were prepared and allowed to recover for 16 wk before study. Animals with chronic infarction exhibited marked cardiac hypertrophy and signs of heart failure, as indicated by a nearly twofold increase in heart weight- and lung weight-to-body weight ratios, respectively, compared with time-matched controls. Cardiac hypertrophy was also evident by a 49% increase in whole cell capacitance of isolated left ventricular myocytes ( P < 0.05). Voltage-clamp experiments revealed that the maximum density of the Ca2+-independent, transient outward current ( I to), measured at +60 mV, was 42% less in myocytes from infarcted hearts than in myocytes from control hearts ( P < 0.05), whereas the inward rectifier current ( I K1) density was not different between groups. The reduced I to density in the infarcted group was reversed, however, in 4–5 h by treatment with exogenous dichloroacetate or pyruvate, both activators of pyruvate dehydrogenase. Moreover, control myocytes incubated for 6 h in the presence of an inhibitor of pyruvate dehydrogenase, 3-bromopyruvate, exhibited a concentration-dependent decrease in I to density compared with untreated cells. The present data demonstrate that I to density is reversibly decreased in surviving myocytes from infarcted hearts and suggest that mechanisms related to glucose metabolism via pyruvate dehydrogenase may be involved. These postinfarction changes in myocyte I to channel function may relate to impaired contractility and arrhythmogenesis, which are characteristic of the intact, failing heart.

scholarly journals Effects of Angiotensin II Type 1 Receptor Antagonist, YM358, on Cardiac Hypertrophy and Dysfunction after Myocardial Infarction in Rats

2002 ◽  
Vol 25 (7) ◽  
pp. 857-860 ◽  
Author(s):  
Tomoko Tokioka-Akagi ◽  
Akira Fujimori ◽  
Masayuki Shibasaki ◽  
Yasuko Matsuda-Satoh ◽  
Osamu Inagaki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Receptor Antagonist

scholarly journals MyD88 mediated inflammatory signaling leads to CaMKII oxidation, cardiac hypertrophy and death after myocardial infarction

2012 ◽  
Vol 52 (5) ◽  
pp. 1135-1144 ◽  
Author(s):  
Madhu V. Singh ◽  
Paari D. Swaminathan ◽  
Elizabeth D. Luczak ◽  
W. Kutschke ◽  
Robert M. Weiss ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Inflammatory Signaling

Abstract 12117: The Cardioprotection of Trimetazidine Against Ischemic Injury is Mediated by AMPK and ERK Signaling Pathway

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Zhenling Liu ◽  
Yina Ma ◽  
Michelle Kuznicki ◽  
Xingchi Chen ◽  
Wanqing Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Oxidation ◽  
Ex Vivo ◽  
Ischemic Injury ◽  
Erk Signaling ◽  
Acid Oxidation ◽  
Ampk Signaling ◽  
Heart Perfusion

Introduction: Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. Hypothesis: AMP-activated protein kinase (AMPK) is an energy sensor that control ATP supply from substrate metabolism and protect heart from energy stress. TMZ changes the cardiac AMP/ATP ratio via modulating fatty acid oxidation, thereby it may trigger AMPK signaling cascade that contribute to protection heart from ischemia/reperfusion (I/R) injury. Methods: The mouse in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) were used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p<0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p<0.05). Intriguingly, the administration of ERK inhibitor, PD 98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Conclusions: Both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.

Active renin and angiotensinogen in cardiac interstitial fluid after myocardial infarction

1999 ◽  
Vol 276 (6) ◽  
pp. H1818-H1826 ◽  
Author(s):  
Alan T. Hirsch ◽  
John A. Opsahl ◽  
Mary M. Lunzer ◽  
Stephen A. Katz
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Infarct Size ◽  
Interstitial Fluid ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Active Renin

The renin-angiotensin system promotes cardiac hypertrophy after myocardial infarction. The purpose of this study was to measure renin and angiotensinogen in plasma and myocardium 10 days after myocardial infarction. Infarction involving 45 ± 4% of left ventricular circumference with accompanying hypertrophy was induced in rats ( n = 14). Plasma and myocardial renin were increased after infarction compared with sham controls ( n = 8) (27.4 ± 3.2 vs. 7.5 ± 1.8 ng ANG I ⋅ ml plasma ⋅ h−1, P < 0.0002; and 8.8 ± 1.6 vs. 2.5 ± 0.1 ng ANG I ⋅ g myocardium−1 ⋅ h−1, P < 0.008, respectively). After infarction, myocardial renin was correlated with infarct size ( r = 0.62, P < 0.02) and plasma renin ( r = 0.55, P < 0.04). Plasma angiotensinogen decreased in infarct animals, but myocardial angiotensinogen was not different from shams (1.1 ± 0.08 vs. 2.03 ± 0.06 nM/ml plasma, P < 0.002; and 0.081 ± 0.008 vs. 0.070 ± 0.004 nM/g myocardium, respectively). In conclusion, myocardial renin increased after infarction in proportion to plasma renin and infarct size, and myocardial angiotensinogen was maintained after infarction despite decreased plasma angiotensinogen and increased levels of myocardial renin.

scholarly journals Inhibition of Endogenous Mst1 Prevents Apoptosis and Cardiac Dysfunction Without Affecting Cardiac Hypertrophy After Myocardial Infarction

2007 ◽  
Vol 100 (9) ◽  
pp. 1344-1352 ◽  
Author(s):  
Mari Odashima ◽  
Soichiro Usui ◽  
Hiromitsu Takagi ◽  
Chull Hong ◽  
Jing Liu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Cardiac Dysfunction

The role of non-coding RNA/microRNAs in cardiac disease

2018 ◽  
Author(s):  
Yolan J. Reckman ◽  
Yigal M. Pinto
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Cardiac Disease ◽  
Cardiac Development ◽  
Rna Transcripts ◽  
The Past ◽  
Non Coding Rna ◽  
Organ Systems ◽  
Non Coding Rnas

In the past two decades, our knowledge about non-coding DNA has increased tremendously. While non-coding DNA was initially discarded as ‘junk DNA’, we are now aware of the important and often crucial roles of RNA transcripts that do not translate into protein. Non-coding RNAs (ncRNAs) play important functions in normal cellular homeostasis and also in many diseases across all organ systems. Among the different ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been studied the most. In this chapter we discuss the role of miRNAs and lncRNAs in cardiac disease. We present examples of miRNAs with fundamental roles in cardiac development (miR-1), hypertrophy (myomiRs, miR-199, miR-1/133), fibrosis (miR-29, miR-21), myocardial infarction (miR-15, miR17~92), and arrhythmias/conduction (miR-1). We provide examples of lncRNAs related to cardiac hypertrophy (MHRT, CHRF), myocardial infarction (ANRIL, MIAT), and arrhythmias (KCNQ1OT1). We also discuss miRNAs and lncRNAs as potential therapeutic targets or biomarkers in cardiac disease.

Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak

2001 ◽  
Vol 280 (4) ◽  
pp. H1762-H1769 ◽  
Author(s):  
Masayuki Taniguchi ◽  
Craig Wilson ◽  
Charlene A. Hunter ◽  
Daniel J. Pehowich ◽  
Alexander S. Clanachan ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Glucose Metabolism ◽  
Pyruvate Dehydrogenase ◽  
Mitochondrial Membrane ◽  
Glucose Oxidation ◽  
Proton Leak ◽  
Cardiac Efficiency ◽  
Cardiac Work ◽  
Atp Production ◽  
Rat Hearts

Dichloroacetate (DCA) is a pyruvate dehydrogenase activator that increases cardiac efficiency during reperfusion of ischemic hearts. We determined whether DCA increases efficiency of mitochondrial ATP production by measuring proton leak in mitochondria from isolated working rat hearts subjected to 30 min of ischemia and 60 min of reperfusion. In untreated hearts, cardiac work and efficiency decreased during reperfusion to 26% and 40% of preischemic values, respectively. Membrane potential was significantly lower in mitochondria from reperfused (175.6 ± 2.2 mV) versus aerobic (185.8 ± 3.1 mV) hearts. DCA (1 mM added at reperfusion) improved recovery of cardiac work (1.9-fold) and efficiency (1.5-fold) but had no effect on mitochondrial membrane potential (170.6 ± 2.9 mV). At the maximal attainable membrane potential, O2consumption (nmol O2 · mg−1 · min−1) did not differ between untreated or DCA-treated hearts (128.3 ± 7.5 and 120.6 ± 7.6, respectively) but was significantly greater than aerobic hearts (76.6 ± 7.6). During reperfusion, DCA increased glucose oxidation 2.5-fold and decreased H+production from glucose metabolism to 53% of untreated hearts. Because H+ production decreases cardiac efficiency, we suggest that DCA increases cardiac efficiency during reperfusion of ischemic hearts by increasing the efficiency of ATP use and not by increasing the efficiency of ATP production.

Sign in / Sign up

Export Citation Format

Share Document