scholarly journals Guidelines for evaluating myocardial cell death

2019 ◽  
Vol 317 (5) ◽  
pp. H891-H922 ◽  
Author(s):  
Paras K. Mishra ◽  
Adriana Adameova ◽  
Joseph A. Hill ◽  
Christopher P. Baines ◽  
Peter M. Kang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Best Practices ◽  
Cardiac Remodeling ◽  
Myocardial Cell ◽  
Autophagic Cell Death ◽  
Multiple Forms ◽  
Regulated Cell Death ◽  
Fundamental Process ◽  
Cell Death Mechanisms

Cell death is a fundamental process in cardiac pathologies. Recent studies have revealed multiple forms of cell death, and several of them have been demonstrated to underlie adverse cardiac remodeling and heart failure. With the expansion in the area of myocardial cell death and increasing concerns over rigor and reproducibility, it is important and timely to set a guideline for the best practices of evaluating myocardial cell death. There are six major forms of regulated cell death observed in cardiac pathologies, namely apoptosis, necroptosis, mitochondrial-mediated necrosis, pyroptosis, ferroptosis, and autophagic cell death. In this article, we describe the best methods to identify, measure, and evaluate these modes of myocardial cell death. In addition, we discuss the limitations of currently practiced myocardial cell death mechanisms. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-evaluating-myocardial-cell-death/ .

Different cell death mechanisms are triggered by acute or chronic right heart failure-induced liver failure

2011 ◽  
Vol 49 (01) ◽  
Author(s):  
K Herzer ◽  
G Kneiseler ◽  
F Post ◽  
M Schlattjan ◽  
T Neumann ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Liver Failure ◽  
Right Heart Failure ◽  
Right Heart ◽  
Cell Death Mechanisms

Abstract P419: A Systematic Characterization of Brain Endothelial Cell Death in Intracerebral Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Maulana Ikhsan ◽  
Marietta Zille
Keyword(s):  
Cell Death ◽  
Intracerebral Hemorrhage ◽  
Brain Tissue ◽  
Vascular Integrity ◽  
Regulated Cell Death ◽  
Injury Mechanisms ◽  
Endothelial Cell Death ◽  
Cell Death Mechanisms ◽  
Underlying Mechanisms

Introduction: Intracerebral hemorrhage (ICH) is a type of stroke caused by the loss of vascular integrity leading to bleeding within the brain tissue. Hematoma-derived factors cause secondary injury mechanisms such as cell death days to weeks after the event and in regions distant from the primary insult. Increasing evidence suggests that hemoglobin released by the hematoma is one of the major contributors to neuronal injury in ICH. To date, it is unclear whether brain endothelial cells (EC) are similarly vulnerable to hemolysis products and undergo regulated cell death. Hypothesis: We hypothesized that brain EC undergo multiple, different modes of cell death after ICH and that the underlying mechanisms are different compared to neurons. Methods: We systematically investigated cell death mechanisms in brain EC after exposure to the hemolysis product hemin. We used chemical inhibitors of apoptosis, autophagy, ferroptosis, necroptosis, and parthanatos and assessed biochemical markers of these cell death modes. Results: Brain EC viability was concentration-dependently decreased, starting at higher hemin concentrations than neurons. Treatment of EC with ferroptosis inhibitors protective against hemin toxicity in neurons and against ICH in vivo showed that only N-acetylcysteine and deferoxamine protected brain EC, while ferrostatin-1 and U0126 did not abrogate EC death. The autophagy inhibitor bafilomycin A1 also reduced EC death and hemin increased the expression of the autophagy marker LC3. While inhibitors against apoptosis and parthanatos were not effective, the necroptosis inhibitor GSK872 demonstrated a partial protective effect. Conclusions: Our data suggest that ICH induces different mechanisms of death in EC (ferroptosis and autophagy) compared to neurons (ferroptosis and necroptosis) and may thus warrant a combinatorial therapeutic approach. Further investigations in human and ovine ICH brain tissue are ongoing.

scholarly journals The Myocardial Unfolded Protein Response during Ischemic Cardiovascular Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Edward B. Thorp
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Ischemic Injury ◽  
Cell Loss ◽  
The Elderly ◽  
Myocardial Cell ◽  
Ageing Population ◽  
Unfolded Protein ◽  
Heart Chamber ◽  
Sequence Of Events

Heart failure is a progressive and disabling disease. The incidence of heart failure is also on the rise, particularly in the elderly of industrialized societies. This is in part due to an increased ageing population, whom initially benefits from improved, and life-extending cardiovascular therapy, yet ultimately succumb to myocardial failure. A major cause of heart failure is ischemia secondary to the sequence of events that is dyslipidemia, atherosclerosis, and myocardial infarction. In the case of heart failure postmyocardial infarction, ischemia can lead to myocardial cell death by both necrosis and apoptosis. The extent of myocyte death postinfarction is associated with adverse cardiac remodeling that can contribute to progressive heart chamber dilation, ventricular wall thinning, and the onset of loss of cardiac function. In cardiomyocytes, recent studies indicate that myocardial ischemic injury activates the unfolded protein stress response (UPR) and this is associated with increased apoptosis. This paper focuses on the intersection of ischemia, the UPR, and cell death in cardiomyocytes. Targeting of the myocardial UPR may prove to be a viable target for the prevention of myocyte cell loss and the progression of heart failure due to ischemic injury.

scholarly journals Expression of Concern: Myocardial cell death and regeneration during progression of cardiac hypertrophy to heart failure.

2020 ◽  
Vol 295 (10) ◽  
pp. 3386-3386
Author(s):  
Sagartirtha Sarkar ◽  
Mamta Chawla-Sarkar ◽  
David Young ◽  
Kazutoshi Nishiyama ◽  
Mary E. Rayborn ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Cardiac Hypertrophy ◽  
Myocardial Cell

scholarly journals Simultaneous polychromatic flow cytometric detection of multiple forms of regulated cell death

APOPTOSIS ◽  
2019 ◽  
Vol 24 (5-6) ◽  
pp. 453-464 ◽  
Author(s):  
D. Bergamaschi ◽  
A. Vossenkamper ◽  
W. Y. J. Lee ◽  
P. Wang ◽  
E. Bochukova ◽  
...  
Keyword(s):  
Cell Death ◽  
Multiple Forms ◽  
Flow Cytometric ◽  
Regulated Cell Death

Abstract 85: A Novel Mitochondrial Targeted Fusion Protein Containing Endonuclease III Protects the Heart Against Myocardial Infarction and Pressure Overload Heart Failure

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jessica M Bradley ◽  
Hiroyuki Otsuka ◽  
Chelsea L Organ ◽  
Shashi Bhushan ◽  
David J Polhemus ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Fusion Protein ◽  
Myocardial Cell ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Myocardial Infarct Size ◽  
Ventricular Ejection Fraction ◽  
Endonuclease Iii ◽  
Mtdna Repair

Background: Oxidative stress is a primary cause of mitochondrial DNA (mtDNA) damage and plays a role in myocardial cell death. mtDNA repair enzymes are crucial for mtDNA repair and cell survival. We tested the efficacy of a novel, mitochondrial targeted fusion protein that traffics Endonuclease III (Exscien1-III) in murine models of myocardial ischemia/reperfusion (MI/R) injury and transverse aortic constriction (TAC) heart failure (HF). We previously demonstrated that Exscien1-III administered at R reduced myocardial infarct size and preserved left ventricular ejection fraction (LVEF) following MI/R. We hypothesized that delayed administration of Exscien1-III would promote mtDNA repair and protect the myocardium against MI/R and TAC heart failure. Methods: Male C57/BL6J (10-12 wks) were subjected to 45 min of MI and 24 hrs of R. Exscien1-III (4 mg/kg, i.p., n=13) or vehicle (VEH, n=13) was administered 30 min after R. Male C57/BL6J were subjected to TAC (27 g needle) and Exscien1-III (4 mg/kg/d, i.p., n=10) or VEH (n=6) were administered starting at 3 wks post TAC. Echocardiography was performed at baseline and following TAC to assess LVEF. Results: Exscien1-III reduced myocardial INF/AAR by 24% (p < 0.05 vs. VEH). Exscien1-III preserved LVEF (49.1 ± 4.0% vs. 32.9 ± 3.2%, p < 0.01) and reduced LV dilation (LVEDD/LVESD; 3.8/2.8 vs. 4.4/3.4, p < 0.05) at 8 wks compared to vehicle. Conclusion: These results demonstrate that delayed administration of Exscien1-III significantly attenuates myocardial cell death and preserves LV function in acute MI and HF. Studies are currently underway to define the molecular mechanisms involved in Exscien1-III induced cardioprotection.

scholarly journals Myocardial Cell Death and Regeneration during Progression of Cardiac Hypertrophy to Heart Failure

2004 ◽  
Vol 279 (50) ◽  
pp. 52630-52642 ◽  
Author(s):  
Sagartirtha Sarkar ◽  
Mamta Chawla-Sarkar ◽  
David Young ◽  
Kazutoshi Nishiyama ◽  
Mary E. Rayborn ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Death ◽  
Cardiac Hypertrophy ◽  
Disease Process ◽  
Myocardial Damage ◽  
Myocardial Cell ◽  
Mouse Heart ◽  
Ki 67 ◽  
End Stage Heart Failure ◽  
End Stage

Cardiac hypertrophy and ensuing heart failure are among the most common causes of mortality worldwide, yet the triggering mechanisms for progression of hypertrophy to failure are not fully understood. Tissue homeostasis depends on proper relationships between cell proliferation, differentiation, and death and any imbalance between them results in compromised cardiac function. Recently, we developed a transgenic (Tg) mouse model that overexpress myotrophin (a 12-kDa protein that stimulates myocyte growth) in heart resulting in hypertrophy that progresses to heart failure. This provided us an appropriate model to study the disease process at any point from initiation of hypertrophy end-stage heart failure. We studied detailed apoptotic signaling and regenerative pathways and found that the Tg mouse heart undergoes myocyte loss and regeneration, but only at a late stage (during transition to heart failure). Several apoptotic genes were up-regulated in 9-month-old Tg hearts compared with age-matched wild type or 4-week-old Tg hearts. Cardiac cell death during heart failure involved activation of Fas, tumor necrosis factor-α, and caspases 9, 8, and 3 and poly(ADP-ribose) polymerase cleavage. Tg mice with hypertrophy associated with compromised functionshowedsignificantup-regulationofcyclins,cyclin-dependent kinases (Cdks), and cell regeneration markers in myocytes. Furthermore, in human failing and nonfailing hearts, similar observations were documented including induction of active caspase 3 and Ki-67 proteins in dilated cardiomyopathic myocytes. Taken together, our data suggest that the stress of extensive myocardial damage from longstanding hypertrophy may cause myocytes to reenter the cell cycle. We demonstrate, for the first time in an animal model, that cell death and regeneration occur simultaneously in myocytes during end-stage heart failure, a phenomenon not observed at the onset of the disease process.

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