scholarly journals Mitophagy Regulation Following Myocardial Infarction

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 199
Author(s):  
Annie Turkieh ◽  
Yara El Masri ◽  
Florence Pinet ◽  
Emilie Dubois-Deruy
Keyword(s):  
Myocardial Infarction ◽  
Cell Death ◽  
Aortic Stenosis ◽  
Cardiac Dysfunction ◽  
Physiological Condition ◽  
Ischemia And Reperfusion ◽  
Interacting Protein ◽  
Selective Elimination

Mitophagy, which mediates the selective elimination of dysfunctional mitochondria, is essential for cardiac homeostasis. Mitophagy is regulated mainly by PTEN-induced putative kinase protein-1 (PINK1)/parkin pathway but also by FUN14 domain-containing 1 (FUNDC1) or Bcl2 interacting protein 3 (BNIP3) and BNIP3-like (BNIP3L/NIX) pathways. Several studies have shown that dysregulated mitophagy is involved in cardiac dysfunction induced by aging, aortic stenosis, myocardial infarction or diabetes. The cardioprotective role of mitophagy is well described, whereas excessive mitophagy could contribute to cell death and cardiac dysfunction. In this review, we summarize the mechanisms involved in the regulation of cardiac mitophagy and its role in physiological condition. We focused on cardiac mitophagy during and following myocardial infarction by highlighting the role and the regulation of PI NK1/parkin-; FUNDC1-; BNIP3- and BNIP3L/NIX-induced mitophagy during ischemia and reperfusion.

scholarly journals Role of Selected miRNAs as Diagnostic and Prognostic Biomarkers in Cardiovascular Diseases, Including Coronary Artery Disease, Myocardial Infarction and Atherosclerosis

2021 ◽  
Vol 8 (2) ◽  
pp. 22
Author(s):  
Rashid Mir ◽  
Imadeldin Elfaki ◽  
Naina Khullar ◽  
Ajaz Ahmad Waza ◽  
Chandan Jha ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Diseases ◽  
Cardiac Dysfunction ◽  
Heart Diseases ◽  
Prognostic Biomarkers ◽  
Apoptotic Bodies ◽  
Artery Disease

Cardiovascular diseases are the leading cause of death worldwide in different cohorts. It is well known that miRNAs have a crucial role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. MiRNAs also have been reported to be associated with cardiac reactions, leading to myocardial infarction (MCI) and ultimately heart failure (HF). To prevent these heart diseases, proper and timely diagnosis of cardiac dysfunction is pivotal. Though there are many symptoms associated with an irregular heart condition and though there are some biomarkers available that may indicate heart disease, authentic, specific and sensitive markers are the need of the hour. In recent times, miRNAs have proven to be promising candidates in this regard. They are potent biomarkers as they can be easily detected in body fluids (blood, urine, etc.) due to their remarkable stability and presence in apoptotic bodies and exosomes. Existing studies suggest the role of miRNAs as valuable biomarkers. A single biomarker may be insufficient to diagnose coronary artery disease (CAD) or acute myocardial infarction (AMI); thus, a combination of different miRNAs may prove fruitful. Therefore, this review aims to highlight the role of circulating miRNA as diagnostic and prognostic biomarkers in cardiovascular diseases such as coronary artery disease (CAD), myocardial infarction (MI) and atherosclerosis.

Programmed Cell Death in Plants: Insights Into developmental and Stress-Induced Cell Death

2021 ◽  
Vol 22 ◽  
Author(s):  
Heba T. Ebeed ◽  
Ahmed A. El-helely
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Plant Development ◽  
Molecular Basis ◽  
Stress Conditions ◽  
Similar Form ◽  
Cellular Homeostasis ◽  
Endogenous Factors ◽  
Selective Elimination

: Programmed cell death (PCD) is a fundamental genetically controlled process in most organisms. PCD is responsible for the selective elimination of damaged or unwanted cells and organs to maintain cellular homeostasis during the organ’s development under normal conditions as well as during defense or adaptation to stressful conditions. PCD pathways have been extensively studied in animals. In plants, studies focusing on understanding the pathways of PCD have advanced significantly. However, the knowledge about the molecular basis of PCD is still very limited. Some PCD pathways that have been discovered in animals are not present in plants or found with a similar form. PCD in plants is developmentally controlled (by endogenous factors) to function in organ development and differentiations as well as environmentally induced (by exogenous stimuli) to help the plant in surviving under stress conditions. Here, we present a review of the role of PCD in plant development and explore different examples of stress-induced PCD as well as highlight the main differences between the plant and animal PCD.

scholarly journals The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction

2020 ◽  
Author(s):  
Liangpeng Li ◽  
Wenbin Fu ◽  
Xue Gong ◽  
Zhi Chen ◽  
Luxun Tang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
G Protein ◽  
Knockout Mice ◽  
Cardiac Dysfunction ◽  
Beclin 1 ◽  
Receptor Kinase ◽  
G Protein Coupled

Abstract Aims G protein-coupled receptor kinase 4 (GRK4) has been reported to play an important role in hypertension, but little is known about its role in cardiomyocytes and myocardial infarction (MI). The goal of present study is to explore the role of GRK4 in the pathogenesis and progression of MI. Methods and results We studied the expression and distribution pattern of GRK4 in mouse heart after MI. GRK4 A486V transgenic mice, inducible cardiomyocyte-specific GRK4 knockout mice, were generated and subjected to MI with their control mice. Cardiac infarction, cardiac function, cardiomyocyte apoptosis, autophagic activity, and HDAC4 phosphorylation were assessed. The mRNA and protein levels of GRK4 in the heart were increased after MI. Transgenic mice with the overexpression of human GRK4 wild type (WT) or human GRK4 A486V variant had increased cardiac infarction, exaggerated cardiac dysfunction and remodelling. In contrast, the MI-induced cardiac dysfunction and remodelling were ameliorated in cardiomyocyte-specific GRK4 knockout mice. GRK4 overexpression in cardiomyocytes aggravated apoptosis, repressed autophagy, and decreased beclin-1 expression, which were partially rescued by the autophagy agonist rapamycin. MI also induced the nuclear translocation of GRK4, which inhibited autophagy by increasing HDAC4 phosphorylation and decreasing its binding to the beclin-1 promoter. HDAC4 S632A mutation partially restored the GRK4-induced inhibition of autophagy. MI caused greater impairment of cardiac function in patients carrying the GRK4 A486V variant than in WT carriers. Conclusion GRK4 increases cardiomyocyte injury during MI by inhibiting autophagy and promoting cardiomyocyte apoptosis. These effects are mediated by the phosphorylation of HDAC4 and a decrease in beclin-1 expression.

scholarly journals PPAR-γ Activation Prevents Septic Cardiac Dysfunction via Inhibition of Apoptosis and Necroptosis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Shiyan Peng ◽  
Junmei Xu ◽  
Wei Ruan ◽  
Suobei Li ◽  
Feng Xiao
Keyword(s):  
Cell Death ◽  
Proinflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
Cardiac Inflammation ◽  
Ppar Γ

Sepsis-induced cardiac dysfunction remains one of the major causes of death in intensive care units. Overwhelmed inflammatory response and unrestrained cell death play critical roles in sepsis-induced cardiac dysfunction. Peroxisome proliferator-activated receptor- (PPAR-) γ has been proven to be cardioprotective in sepsis. However, the mechanism of PPAR-γ-mediated cardioprotection and its relationship with inflammation and cell death are unclear. We hypothesized that activation of PPAR-γ by reducing cardiac inflammation, myocardial apoptosis, and necroptosis may prevent myocardial dysfunction in sepsis. Rats were subjected to cecal ligation and puncture (CLP) with or without PPAR-γ agonist (rosiglitazone) or antagonist T0070907 (T007). After CLP, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated proinflammatory cytokines, and increased apoptosis, necrosis, and necroptosis. This process is corresponded with decreased inhibitor κB (IκBα) and increased NF-κB, receptor-interacting protein kinase-1 (RIP1), RIP3, and mixed lineage kinase-like (MLKL) protein. Activation of PPAR-γ by rosiglitazone pretreatment enhanced PPAR-γ activity and prevented these changes, thereby improving the survival of septic rats. In contrast, inhibition of PPAR-γ by T007 further exacerbated the condition, dropping the survival rate to nearly 0%. In conclusion, PPAR-γ activation by reducing proinflammatory cytokines, apoptosis, and necroptosis in the myocardium prevents septic myocardial dysfunction.

Abstract 341: Akt1 Deletion Promotes Survival in a Model of Spontaneous Myocardial Infarction and Atherosclerosis

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Bethany Kerr ◽  
Lining Ma ◽  
Xiaoxia West ◽  
Nikolay Malinin ◽  
Malory Weber ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Lipid Oxidation ◽  
Cardiac Dysfunction ◽  
Oxidation Products ◽  
Stress Generation ◽  
Foam Cell Formation ◽  
Atherosclerotic Lesions ◽  
Lipid Oxidation Products

The role of Akt1 kinase in cardiac dysfunction and atherosclerosis is hotly contested. Many models use transient Akt1 activation or deletion to study its function in cardiac diseases. The effects of Akt1 knockout were tested in mouse models dependent on short-term Western diets to induce atherosclerotic lesions; however, in these models, the complete cascade ending in infarction does not occur. In contrast, the ApoE -/- /SR-BI -/- double knockout (DKO) mouse represents a model of spontaneous myocardial infarction resulting from severe dyslipidemia and atherosclerosis leading to death between 5-7 weeks of age. In DKO mice and humans, dyslipidemia and inflamed arterial occlusions lead to plaque rupture and myocardial infarction. Importantly, Akt1 activation is dramatically elevated in the myocardium and endothelium of DKO vs. WT mice. To assess the role of chronic Akt1 activation in atherosclerosis, we generated ApoE -/- /SR-BI -/- /Akt1 -/- triple knockout (TKO) mice. We found that TKO mice exhibited decreased cardiac dysfunction and hypertrophy resulting in longer lifespan vs. DKO. In addition, TKO mice have diminished endothelial VCAM expression, decreased atherosclerotic lesions in vivo , and reduced foam cell formation in vitro . ROS production, which is regulated by Akt1 signaling and contributes to atherosclerosis during dyslipidemia, was reduced in TKO hearts, plasma, endothelial cells, and macrophages. This led to reduced proatherogenic lipid oxidation product accumulation in TKO vs. DKO. Moreover, Akt1 deletion in TKO mice decreased levels of CD36, the main oxidized lipid receptor, in hearts, on endothelial cells, and on macrophages. Thus, during dyslipidemia, chronic Akt1 activation results in elevated oxidative stress, generation of proatherogenic lipid oxidation products, and expression of CD36 (a known atherothrombotic regulator) resulting in enhanced atherosclerosis and spontaneous myocardial infarction. Inhibition of Akt1 by genetic deletion results in partial rescue of mice leading to decreased atherosclerosis, improved cardiac function, and elongated lifespan. Continued study of chronic Akt1 activation and its effects on atherosclerosis will enable the development of additional targets for heart disease therapeutics.

scholarly journals ­­LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation

2016 ◽  
Vol 213 (12) ◽  
pp. 2671-2689 ◽  
Author(s):  
Julia Zinngrebe ◽  
Eva Rieser ◽  
Lucia Taraborrelli ◽  
Nieves Peltzer ◽  
Torsten Hartwig ◽  
...  
Keyword(s):  
Cell Death ◽  
Influenza A ◽  
Gene Activation ◽  
Ubiquitin Chain ◽  
Interacting Protein ◽  
Signaling Complex ◽  
Biochemical Level ◽  
Chronic Proliferative Dermatitis ◽  
Tlr3 Signaling

The linear ubiquitin chain assembly complex (LUBAC), consisting of SHANK-associated RH-domain–interacting protein (SHARPIN), heme-oxidized IRP2 ubiquitin ligase-1 (HOIL-1), and HOIL-1–interacting protein (HOIP), is a critical regulator of inflammation and immunity. This is highlighted by the fact that patients with perturbed linear ubiquitination caused by mutations in the Hoip or Hoil-1 genes, resulting in knockouts of these proteins, may simultaneously suffer from immunodeficiency and autoinflammation. TLR3 plays a crucial, albeit controversial, role in viral infection and tissue damage. We identify a pivotal role of LUBAC in TLR3 signaling and discover a functional interaction between LUBAC components and TLR3 as crucial for immunity to influenza A virus infection. On the biochemical level, we identify LUBAC components as interacting with the TLR3-signaling complex (SC), thereby enabling TLR3-mediated gene activation. Absence of LUBAC components increases formation of a previously unrecognized TLR3-induced death-inducing SC, leading to enhanced cell death. Intriguingly, excessive TLR3-mediated cell death, induced by double-stranded RNA present in the skin of SHARPIN-deficient chronic proliferative dermatitis mice (cpdm), is a major contributor to their autoinflammatory skin phenotype, as genetic coablation of Tlr3 substantially ameliorated cpdm dermatitis. Thus, LUBAC components control TLR3-mediated innate immunity, thereby preventing development of immunodeficiency and autoinflammation.

scholarly journals Essential Roles of Receptor-Interacting Protein and TRAF2 in Oxidative Stress-Induced Cell Death

2004 ◽  
Vol 24 (13) ◽  
pp. 5914-5922 ◽  
Author(s):  
Han-Ming Shen ◽  
Yong Lin ◽  
Swati Choksi ◽  
Jamie Tran ◽  
Tian Jin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Tumor Necrosis Factor Receptor ◽  
Membrane Lipid ◽  
Critical Event ◽  
Wild Type ◽  
Embryonic Fibroblasts ◽  
Interacting Protein ◽  
Necrosis Factor

ABSTRACT Oxidative stress and reactive oxygen species (ROS) can elicit and modulate various physiological and pathological processes, including cell death. However, the mechanisms controlling ROS-induced cell death are largely unknown. Data from this study suggest that receptor-interacting protein (RIP) and tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2), two key effector molecules of TNF signaling, are essential for ROS-induced cell death. We found that RIP−/− or TRAF2−/− mouse embryonic fibroblasts (MEF) are resistant to ROS-induced cell death when compared to wild-type cells, and reconstitution of RIP and TRAF2 gene expression in their respective deficient MEF cells restored their sensitivity to H2O2-induced cell death. We also found that RIP and TRAF2 form a complex upon H2O2 exposure, but without the participation of TNFR1. The colocalization of RIP with a membrane lipid raft marker revealed a possible role of lipid rafts in the transduction of cell death signal initiated by H2O2. Finally, our results demonstrate that activation of c-Jun NH2-terminal kinase 1 is a critical event downstream of RIP and TRAF2 in mediating ROS-induced cell death. Therefore, our study uncovers a novel signaling pathway regulating oxidative stress-induced cell death.

scholarly journals 5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction

2021 ◽  
Vol 10 (14) ◽  
pp. 3104
Author(s):  
Sandy Popp ◽  
Angelika Schmitt-Böhrer ◽  
Simon Langer ◽  
Ulrich Hofmann ◽  
Leif Hommers ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Dysfunction ◽  
Inflammatory Cells ◽  
Sham Operation ◽  
Male Mice ◽  
Tnf Α ◽  
Inflammatory Processes ◽  
Knockout Animals ◽  
And Behavior

Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI <30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.

The role of receptor interacting protein kinase 1 (RIPK1) in bile acid-induced pancreatic acinar cell death

Pancreatology ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. S8
Author(s):  
Yulin Ouyang ◽  
S. Voronina ◽  
M. Chvanov ◽  
L. Wen ◽  
D. Latawiec ◽  
...  
Keyword(s):  
Cell Death ◽  
Bile Acid ◽  
Protein Kinase ◽  
Acinar Cell ◽  
Pancreatic Acinar Cell ◽  
Interacting Protein
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