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.

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.

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 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 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.

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 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.

scholarly journals Modern statin therapy in clinical practice: The lower the better

2013 ◽  
Vol 141 (1-2) ◽  
pp. 104-106 ◽  
Author(s):  
Edita Stokic
Keyword(s):  
Heart Disease ◽  
Cardiovascular Risk ◽  
Ischemic Heart Disease ◽  
Statin Therapy ◽  
Meta Analysis ◽  
Ischemic Heart ◽  
Mortality And Morbidity ◽  
Increased Risk ◽  
Coronary Events ◽  
Risk Treatment

Lipid and lipoprotein disorders are well known risk factors for atherosclerosis and its complications. The level of atherogenic LDL-cholesterol (LDL-C) is directly related to an increased risk of occurrence and progression of ischemic heart disease. Epidemiological and clinical studies have shown that the use of statin therapy to decrease LDL-C can significantly reduce the incidence of mortality, major coronary events and the need for revascularization procedures in the different groups of patients. The findings of a large meta-analysis conducted by the Cholesterol Treatment Trialists? (CTT) collaborators showed that every 1.0 mmol/l reduction of atherogenic LDL-C is associated with a 22% reduction in cardiovascular diseases mortality and morbidity. However, despite the impressive results of the benefits of statin therapy, the EUROASPIRE study showed that about 50% of patients with ischemic heart disease did not achieve target LDL-C levels. According to the new ESC/EAS Guidelines for the Management of Dyslipidaemias in patients with a very high cardiovascular risk, treatment goal should be to decrease LDL-C below 1.8 mmol/l or ?50% of initial values. In the majority of patients that can be achieved by statin therapy. For this reason an adequate choice of statins is of crucial importance, whereby the needed reduction in atherogenic LDL-C, after the identification of its target level based on the assessment of total cardiovascular risk, can be achieved.

Repeated intermittent stress exacerbates myocardial ischemia-reperfusion injury

1998 ◽  
Vol 274 (2) ◽  
pp. R470-R475 ◽  
Author(s):  
Deborah A. Scheuer ◽  
Steven W. Mifflin
Keyword(s):  
Heart Disease ◽  
Myocardial Ischemia ◽  
Ischemic Heart Disease ◽  
Infarct Size ◽  
Chronic Stress ◽  
Restraint Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Chronic stress in humans has been correlated with increased risk for ischemic heart disease. Thus experiments were conducted to determine if repeated intermittent restraint stress increased infarct size in a rat model of myocardial ischemia-reperfusion injury. Male Sprague-Dawley rats were subjected to no stress (control) or to daily restraint stress for 1–1.5 h for 8–14 days (stress protocol A) or for 2 h daily for 11 or 12 days (stress protocol B). Myocardial ischemia-reperfusion (30-min ischemia, 3-h reperfusion) was performed in anesthetized rats. Average baseline arterial pressures were 111 ± 4, 120 ± 10, and 125 ± 7 mmHg in the control, stress protocol A, and stress protocol B groups, respectively. Infarct size (%area at risk) was significantly larger in both groups of stressed rats compared with control rats (58 ± 5, 78 ± 2, and 79 ± 3% in the control, stress protocol A, and stress protocol B groups, respectively). During ischemia or early reperfusion, zero of eight control, two of six protocol A stress, and two of five protocol B stress rats had at least one period of severe arrhythmia. Therefore, these results provide experimental evidence corroborating correlative studies in humans that link chronic stress with increased morbidity and mortality from ischemic heart disease.

Coronary Microcirculation in Ischemic Heart Disease

2018 ◽  
Vol 24 (25) ◽  
pp. 2893-2899 ◽  
Author(s):  
Axel R. Pries ◽  
Wolfgang M. Kuebler ◽  
Helmut Habazettl
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Local Level ◽  
Microvascular Permeability ◽  
Coronary Microcirculation ◽  
Ischemic Heart ◽  
Endothelial Glycocalyx ◽  
Microvascular Networks

Background: Ischemic heart disease has long been considered to be exlusively caused by stenosis or occlusion. However, the coronary microcirculation too may play an important role in ischemic conditions. Also, the crucial role of microvessels in not only regulating blood flow on a local level but also mediating vascular permeability or inflammatory responses has been recognized. Objective: To review important physiological and pathophysiological mechanisms of coronary microcirculatory control with focus on heterogeneity of local perfusion, microvascular permeability and inflammation. Method: Selective research of the literature. Results: Heterogeneity is a characteristic of microvascular networks and affects structural and functional parameters such as vessel diameter, length, and connection pattern, flow velocity, wall shear stress, and oxygenation. Microvascular networks are optimized to meet the metabolic demand of all tissue compartments. This requires continuous vascular adaptation regulated by local hemodynamic and metabolic stimuli. Compromising this regulation results in functional arterio-venous shunting and tissue areas with either hyperperfusion or hypoxia in close proximity. In ischemia-reperfusion, increased microvascular permeability may aggravate tissue hypoxia by increasing extravascular pressure and seems to contribute to adverse myocardial remodeling. Transendothelial transport mechanisms and deterioration of the endothelial glycocalyx seem to be major contributors to tissue edema. Also in the context of ischemia-reperfusion, an inflammatory response mediated by venular endothelium expressing specific adhesion molecules contributes to tissue injury. However, anti-inflammatory therapies failed in clinical studies and a multi-targeted approach for cardiac protection is required. Conclusion: Disturbances of the coronary microcirculation are involved in different pathophysiological aspects of reperfusion injury.

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