scholarly journals From Brain to Heart: Possible Role of Amyloid-β in Ischemic Heart Disease and Ischemia-Reperfusion Injury

2020 ◽  
Vol 21 (24) ◽  
pp. 9655
Author(s):  
Giulia Gagno ◽  
Federico Ferro ◽  
Alessandra Lucia Fluca ◽  
Milijana Janjusevic ◽  
Maddalena Rossi ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Reperfusion Injury ◽  
Coronary Atherosclerosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Amyloid Β ◽  
Ischemic Heart ◽  
Amyloid Angiopathy

Ischemic heart disease (IHD) is among the leading causes of death in developed countries. Its pathological origin is traced back to coronary atherosclerosis, a lipid-driven immuno-inflammatory disease of the arteries that leads to multifocal plaque development. The primary clinical manifestation of IHD is acute myocardial infarction (AMI),) whose prognosis is ameliorated with optimal timing of revascularization. Paradoxically, myocardium re-perfusion can be detrimental because of ischemia-reperfusion injury (IRI), an oxidative-driven process that damages other organs. Amyloid-β (Aβ) plays a physiological role in the central nervous system (CNS). Alterations in its synthesis, concentration and clearance have been connected to several pathologies, such as Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). Aβ has been suggested to play a role in the pathogenesis of IHD and cerebral IRI. The purpose of this review is to summarize what is known about the pathological role of Aβ in the CNS; starting from this evidence, we will illustrate the role played by Aβ in the development of coronary atherosclerosis and its possible implications in the pathophysiology of IHD and myocardial IRI. Better elucidation of Aβ’s contribution to the molecular pathways underlying IHD and IRI could be of great help in developing new therapeutic strategies.

scholarly journals The mechanism of miR-525-5p derived from hypoxia and reoxygenation in H9c2 Cardiomyocytes

2022 ◽  
Vol 67 (4) ◽  
pp. 18-23
Author(s):  
Shanshan Wang ◽  
Xin Mei ◽  
Song Ronggang ◽  
Meng Hongyan ◽  
Wei Xinfen
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Reperfusion Injury ◽  
Mrna Expression ◽  
Gene Mutation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Heart ◽  
H9c2 Cells ◽  
H9c2 Cardiomyocytes

Ischemia-reperfusion injury (IRI) is associated with ischemic heart disease (IHD) which leads to patients a poor progression. According to Pubmed Datasets, we analyzed different gene and mRNA expressions in IHD patients with IRI. The relevant mRNA expression detected in H9C2 cells undergo hypoxia and reoxygenation, we selected and structured miR-525-5p gene mutation H9C2 cells, the results performed miR-525-5p mutated restored H9C2 metabolism of mitochondria which detected by relevant genes and proteins. At the same time, miR-525-5p silence resisted hypoxia and reoxygenation induced H9C2 cells apoptosis. All the results indicated miR-525-5p maybe protect H9C2 cells without hypoxia and reoxygenation induced injury through regulating the mitochondria metabolism.

Exosomes: promising sacks for treating ischemic heart disease?

2017 ◽  
Vol 313 (3) ◽  
pp. H508-H523 ◽  
Author(s):  
Gui-Hao Chen ◽  
Jun Xu ◽  
Yue-Jin Yang
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Regeneration ◽  
Ischemic Heart ◽  
Advantages And Disadvantages ◽  
Developing Heart ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Ischemic heart disease(IHD) is the leading cause of death worldwide. Despite the development of continuously improving therapeutic strategies, morbidity and mortality of patients with IHD remain relatively high. Exosomes are a subpopulation of vesicles that are universally recognized as major mediators in intercellular communication. Numerous preclinical studies have shown that these tiny vesicles were protective in IHD, through such actions as alleviating myocardial ischemia-reperfusion injury, promoting angiogenesis, inhibiting fibrosis, and facilitating cardiac regeneration. Our review focused on these beneficial exosome-mediated processes. In addition, we discuss in detail how to fully exploit the therapeutic potentials of exosomes in the field of IHD. Topics include identifying robust sources of exosomes, loading protective agents into exosomes, developing heart-specific exosomes, optimizing isolation methods, and translating the cardioprotective effects of exosomes into clinical practice. Finally, both the advantages and disadvantages of utilizing exosomes in clinical settings are addressed.

Abstract 54: Probenecid Improves Myocardial Function in an Ischemic Heart Disease Murine Model

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Nathan Robbins ◽  
Sheryl E Koch ◽  
Min Jiang ◽  
Michael Tranter ◽  
Xiaoping Ren ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Infarct Size ◽  
Cell Viability ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Heart ◽  
Transient Receptor Potential Vanilloid ◽  
High Concentrations

Introduction Probenecid, previously used for the treatment of gout, is a transient receptor potential vanilloid 2 (TRPV2) agonist. We have found TRPV2 in murine cardiomyocytes and when stimulated by probenecid, results in a positive inotropic response through Ca 2+ influx independent of β-adrenergic signaling. Our hypothesis is that probenecid will increase contractility without affecting cell survival. Methods We studied the role of probenecid as a positive inotrope in a mouse model of ischemic heart disease. We administered probenecid via intraperitoneal injections (100mg/kg) before and after ischemia/reperfusion injury (I/R) and orally via treated water (100mg/kg daily for 4 weeks), using saline injections and untreated water as respective controls. Ischemia was induced by a 45 minute ligation of the LAD followed by reperfusion and all mice were followed serially via echocardiography. We also evaluated the effects of probenecid on HL-1 cell apoptosis by conducting cell viability assays. Results Treatment with probenecid before I/R had no effect on subsequent infarct size (51.6±3.71% vs. 53.4±1.54%;P=NS). However, post-I/R probenecid caused an increase in ejection fraction (EF) of 10.9±1.98% in mice with initial EF between 40-50% (n=6; P<0.01) and 7.28±1.63% in mice with higher initial EF (50-60%) (n=6; p<0.01). Echocardiographic analysis of mice with oral probenecid after I/R demonstrated higher EF and smaller diastolic volume (47.19±2.29%; 79.57mL±1.63; n=6) compared to untreated mice (43.67±2.91%; 89.05mL±5.67; n=6). Cell viability assays showed high concentrations of probenecid had minimal effect on cell viability (88.6±6.2% of control) whereas treatment with high concentrations of isoproterenol (10mM) greatly decreased cell viability (6.7±0.1% of control). Conclusions These experiments demonstrate 1) probenecid increases myocardial contractility at baseline and significantly more so after I/R injury; 2) probenecid therapy improves function when used chronically; 3) the increase in contractility is not associated with either increased infarct size in vivo or apoptosis in vitro. Thus, unlike other positive inotropes, such as isoproterenol, probenecid increases contractility without resulting in significant cell death.

Abstract 204: Modification of AIFm2 By 4HNE Leads to Retrograde Stress Signaling During Ischemia- Reperfusion Injury in Heart

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Sudha Sharma ◽  
Susmita Bhattarai ◽  
Utsab Subedi ◽  
Christina Acosta ◽  
Hosne Ara ◽  
...  
Keyword(s):  
Protein Expression ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Adaptor Protein ◽  
Ischemic Heart ◽  
Spectrometric Analysis ◽  
Apoptosis Inducing Factor ◽  
First Time

Myocardial infarction is a leading cause of death worldwide and occurs due to blockage in blood supply to the heart. Re-establishment of blood flow after a brief period of ischemia leads to paradoxical exacerbation of the cardiomyocyte and its death. This phenomenon is known as ischemia-reperfusion injury. Major evidence in the pathogenesis of ischemia-reperfusion injury is due to oxidative stress, which is an imbalance between reactive oxygen species (ROS) and antioxidants. Membrane consisting of polyunsaturated fatty acid is attacked by ROS leading to lipid peroxidation and the generation of one of the toxic aldehydes 4-hydroxynonenal (4-HNE). Evidence suggests that 4-HNE increases during an ischemia-reperfusion injury in the heart. Apoptosis-inducing factor, mitochondrion-associated 2 (AIFM2) is a mitochondrial located oxidoreductase that participates in caspase-independent apoptosis. In this study, we sought to identify the role of 4-HNE in regulating AIFm2 translocation and cardiomyocyte death during an ischemia-reperfusion injury in the heart. Following ischemia both RNA and protein expression of AIFm2 significantly increased in the ischemic heart compared to sham. Also, 4-HNE adducted AIFm2 translocated from mitochondria to the nucleus shown by western blot analysis in ischemic heart. The mass spectrometric analysis was done to see the modification site on AIFm2 by 4-HNE and revealed that His 174 and Cys 187 are two sites on AIFm2 where 4-HNE adduction occurred. To identify the modification site responsible for AIFm2 translocation we performed site-direct mutagenesis in H9C2 cardiomyocyte, where Histidine 174 was replaced by arginine and Cys 187 was replaced by threonine. When the ischemia-reperfusion injury was induced, only Histidine 174 mutant failed to translocate to the nucleus indicating His 174 modification by 4-HNE was responsible for AIFm2 translocation. To further support the transport mechanism, protein expression of Importin; an adaptor protein responsible for the transfer of proteins to the nucleus was increased in the ischemic heart compared to sham. Collectively, those results for the first time identify the unique role of 4-HNE modification on AIFm2 protein during an ischemia-reperfusion injury in the heart.

scholarly journals Mitophagy in Cardiomyocytes and in Platelets: A Major Mechanism of Cardioprotection Against Ischemia/Reperfusion Injury

Physiology ◽  
2018 ◽  
Vol 33 (2) ◽  
pp. 86-98 ◽  
Author(s):  
Weilin Zhang ◽  
Chuyan Chen ◽  
Jun Wang ◽  
Lei Liu ◽  
Yubin He ◽  
...  
Keyword(s):  
Heart Disease ◽  
Reperfusion Injury ◽  
Cellular Response ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Molecular Regulation ◽  
Major Mechanism

Mitophagy, a process that selectively removes damaged organelles by autolysosomal degradation, is an early cellular response to ischemia. Mitophagy is activated in both cardiomyocytes and platelets during ischemia/reperfusion (I/R) and heart disease conditions. We focus on the molecular regulation of mitophagy and highlight the role of mitophagy in cardioprotection.

scholarly journals Targeting Ferroptosis against Ischemia/Reperfusion Cardiac Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 667
Author(s):  
José Lillo-Moya ◽  
Catalina Rojas-Solé ◽  
Diego Muñoz-Salamanca ◽  
Emiliano Panieri ◽  
Luciano Saso ◽  
...  
Keyword(s):  
Blood Flow ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Ischemic Heart ◽  
Myocardial Infarct Size

Ischemic heart disease is a leading cause of death worldwide. Primarily, ischemia causes decreased oxygen supply, resulting in damage of the cardiac tissue. Naturally, reoxygenation has been recognized as the treatment of choice to recover blood flow through primary percutaneous coronary intervention. This treatment is the gold standard therapy to restore blood flow, but paradoxically it can also induce tissue injury. A number of different studies in animal models of acute myocardial infarction (AMI) suggest that ischemia-reperfusion injury (IRI) accounts for up to 50% of the final myocardial infarct size. Oxidative stress plays a critical role in the pathological process. Iron is an essential mineral required for a variety of vital biological functions but also has potentially toxic effects. A detrimental process induced by free iron is ferroptosis, a non-apoptotic type of programmed cell death. Accordingly, efforts to prevent ferroptosis in pathological settings have focused on the use of radical trapping antioxidants (RTAs), such as liproxstatin-1 (Lip-1). Hence, it is necessary to develop novel strategies to prevent cardiac IRI, thus improving the clinical outcome in patients with ischemic heart disease. The present review analyses the role of ferroptosis inhibition to prevent heart IRI, with special reference to Lip-1 as a promising drug in this clinicopathological context.

scholarly journals New Insights Into the Role of Mitochondria Quality Control in Ischemic Heart Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Yanguo Xin ◽  
Xiaodong Zhang ◽  
Jingye Li ◽  
Hui Gao ◽  
Jiayu Li ◽  
...  
Keyword(s):  
Quality Control ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Ischemic Heart ◽  
Mortality And Morbidity ◽  
Energy Deprivation

IHD is a significant cause of mortality and morbidity worldwide. In the acute phase, it's demonstrated as myocardial infarction and ischemia-reperfusion injury, while in the chronic stage, the ischemic heart is mainly characterised by adverse myocardial remodelling. Although interventions such as thrombolysis and percutaneous coronary intervention could reduce the death risk of these patients, the underlying cellular and molecular mechanisms need more exploration. Mitochondria are crucial to maintain the physiological function of the heart. During IHD, mitochondrial dysfunction results in the pathogenesis of ischemic heart disease. Ischemia drives mitochondrial damage not only due to energy deprivation, but also to other aspects such as mitochondrial dynamics, mitochondria-related inflammation, etc. Given the critical roles of mitochondrial quality control in the pathological process of ischemic heart disease, in this review, we will summarise the efforts in targeting mitochondria (such as mitophagy, mtROS, and mitochondria-related inflammation) on IHD. In addition, we will briefly revisit the emerging therapeutic targets in this field.

scholarly journals Botanical Flavonoids on Coronary Heart Disease

2011 ◽  
Vol 39 (04) ◽  
pp. 661-671 ◽  
Author(s):  
Chong-Zhi Wang ◽  
Sangeeta R. Mehendale ◽  
Tyler Calway ◽  
Chun-Su Yuan
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Herbal Medicines ◽  
Grape Seed ◽  
Ischemic Heart ◽  
Care Costs

Ischemic heart disease (IHD) is one of the leading causes of death in Western countries. Prevention rather than treatment of heart disease can significantly improve patients' quality of life and reduce health care costs. Flavonoids are widely distributed in vegetables, fruits and herbal medicines. Regularly consuming botanicals, especially those containing flavonoids, has been associated with a reduction in cardiovascualar disease; thus, it is important to investigate how flavonoids improve cardiac resistance to heart disease and their related mechanisms of action. It has been shown that cardiomyocyte injury and death can result from ischemia-reperfusion, which is pathognomonic of ischemic heart disease. Massive reactive oxygen species (ROS) release at the onset of reperfusion produces cell injury and death. "Programming" the heart to either generate less ROS or to increase strategic ROS removal could reduce reperfusion response. Additionally, profuse nitric oxide (NO) release at reperfusion could be protective in "preconditioning" models. Botanical flavonoids induce preconditioning of the heart, thereby protecting against ischemia-reperfusion injury. In this article, we will discuss two herbs containing potent flavonoids, Scutellaria baicalensis and grape seed proanthocyanidin, which can potentially offer cardiac protection against ischemic heart disease.

scholarly journals The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Lukas J. Motloch ◽  
Jun Hu ◽  
Fadi G. Akar
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Anion Channel ◽  
Permeability Transition ◽  
Ischemic Heart ◽  
Translocator Protein ◽  
Acute Ischemia ◽  
Organ Systems

Mitochondrial dysfunction is a hallmark of multiple cardiovascular disorders, including ischemic heart disease. Although mitochondria are well recognized for their role in energy production and cell death, mechanisms by which they control excitation-contraction coupling, excitability, and arrhythmias are less clear. The translocator protein (TSPO) is an outer mitochondrial membrane protein that is expressed in multiple organ systems. The abundant expression of TSPO in macrophages has been leveraged to image the immune response of the heart to inflammatory processes. More recently, the recognition of TSPO as a regulator of energy-dissipating mitochondrial pathways has extended its utility from a diagnostic marker of inflammation to a therapeutic target influencing diverse pathophysiological processes. Here, we provide an overview of the emerging role of TSPO in ischemic heart disease. We highlight the importance of TSPO in the regenerative process of reactive oxygen species (ROS) induced ROS release through its effects on the inner membrane anion channel (IMAC) and the permeability transition pore (PTP). We discuss evidence implicating TSPO in arrhythmogenesis in the settings of acute ischemia-reperfusion injury and myocardial infarction.

Sign in / Sign up

Export Citation Format

Share Document