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Cardiovascular Research Jun 2019
Topics: Animals; Cardiovascular Agents; Extracellular Vesicles; Humans; Ischemic Preconditioning; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Paracrine Communication; Platelet Activation; Signal Transduction; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling
PubMed: 30865272
DOI: 10.1093/cvr/cvz072 -
Hellenic Journal of Cardiology : HJC =... 2019The management of ST-segment elevation myocardial infarction (STEMI) has evolved significantly over the last decades. STEMI treatment includes reperfusion therapy,... (Review)
Review
The management of ST-segment elevation myocardial infarction (STEMI) has evolved significantly over the last decades. STEMI treatment includes reperfusion therapy, ideally by primary percutaneous coronary intervention (pPCI), modern antithrombotic therapy and secondary prevention measures. Even though many areas in the management of STEMI are well studied and analyzed in the guidelines, there are still challenges and unanswered questions on how to improve outcomes. This review aims to offer an insight in areas that need to be explored.
Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Cyclosporine; Female; Humans; Hypothermia; Male; Middle Aged; Mitochondria, Heart; Myocardial Reperfusion; Percutaneous Coronary Intervention; Platelet Membrane Glycoproteins; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Secondary Prevention; Thrombolytic Therapy; Time Factors; Treatment Outcome; Vasodilator Agents
PubMed: 30639352
DOI: 10.1016/j.hjc.2019.01.001 -
Molecules (Basel, Switzerland) Apr 2022Ischemia-reperfusion myocardial damage is a paradoxical tissue injury occurring during percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI)... (Review)
Review
Ischemia-reperfusion myocardial damage is a paradoxical tissue injury occurring during percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients. Although this damage could account for up to 50% of the final infarct size, there has been no available pharmacological treatment until now. Oxidative stress contributes to the underlying production mechanism, exerting the most marked injury during the early onset of reperfusion. So far, antioxidants have been shown to protect the AMI patients undergoing PCI to mitigate these detrimental effects; however, no clinical trials to date have shown any significant infarct size reduction. Therefore, it is worthwhile to consider multitarget antioxidant therapies targeting multifactorial AMI. Indeed, this clinical setting involves injurious effects derived from oxygen deprivation, intracellular pH changes and increased concentration of cytosolic Ca and reactive oxygen species, among others. Thus, we will review a brief overview of the pathological cascades involved in ischemia-reperfusion injury and the potential therapeutic effects based on preclinical studies involving a combination of antioxidants, with particular reference to resveratrol and quercetin, which could contribute to cardioprotection against ischemia-reperfusion injury in myocardial tissue. We will also highlight the upcoming perspectives of these antioxidants for designing future studies.
Topics: Antioxidants; Humans; Myocardial Infarction; Myocardial Reperfusion Injury; Percutaneous Coronary Intervention; Quercetin; Reperfusion Injury; Resveratrol
PubMed: 35458766
DOI: 10.3390/molecules27082564 -
Biomedicine & Pharmacotherapy =... Jun 2024Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD synthesis, has been discovered...
Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway.
Topics: Animals; Myocardial Reperfusion Injury; Sirtuin 3; Signal Transduction; Male; Niacinamide; Superoxide Dismutase; Rats, Sprague-Dawley; Rats; Apoptosis; Oxidative Stress; Pyridinium Compounds; Myocytes, Cardiac; Reactive Oxygen Species; Cell Line; Cardiotonic Agents; Sirtuins
PubMed: 38703508
DOI: 10.1016/j.biopha.2024.116689 -
British Journal of Pharmacology Apr 2015Cardiomyocyte cell death occurring during myocardial reperfusion (reperfusion injury) contributes to final infarct size after transient coronary occlusion. Different... (Review)
Review
Cardiomyocyte cell death occurring during myocardial reperfusion (reperfusion injury) contributes to final infarct size after transient coronary occlusion. Different interrelated mechanisms of reperfusion injury have been identified, including alterations in cytosolic Ca(2+) handling, sarcoplasmic reticulum-mediated Ca(2+) oscillations and hypercontracture, proteolysis secondary to calpain activation and mitochondrial permeability transition. All these mechanisms occur during the initial minutes of reperfusion and are inhibited by intracellular acidosis. The cGMP/PKG pathway modulates the rate of recovery of intracellular pH, but has also direct effect on Ca(2+) oscillations and mitochondrial permeability transition. The cGMP/PKG pathway is depressed in cardiomyocytes by ischaemia/reperfusion and preserved by ischaemic postconditioning, which importantly contributes to postconditioning protection. The present article reviews the mechanisms and consequences of the effect of ischaemic postconditioning on the cGMP/PKG pathway, the different pharmacological strategies aimed to stimulate it during myocardial reperfusion and the evidence, limitations and promise of translation of these strategies to the clinical practice. Overall, the preclinical and clinical evidence suggests that modulation of the cGMP/PKG pathway may be a therapeutic target in the context of myocardial infarction.
Topics: Animals; Cardiotonic Agents; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Humans; Myocardial Reperfusion Injury; Signal Transduction
PubMed: 25297462
DOI: 10.1111/bph.12959 -
Advances in Clinical and Experimental... Feb 2023Ferroptosis is a type of iron-dependent programmed cell death. The inhibition of ferroptosis has been reported to alleviate myocardial ischemia/reperfusion injury (IRI)....
BACKGROUND
Ferroptosis is a type of iron-dependent programmed cell death. The inhibition of ferroptosis has been reported to alleviate myocardial ischemia/reperfusion injury (IRI). However, it is unknown whether this protective effect occurs in the ischemia or reperfusion phase. Sestrin 1 (Sesn1) possesses remarkable cytoprotective functions to diverse cellular stresses. However, whether Sesn1 is involved in the regulatory process of ferroptosis during myocardial IRI is unknown.
OBJECTIVES
This study aimed to simulate an acute myocardial infarction (AMI) that occurs in rats within 6 h, verify the occurrence and effects of ferroptosis in the phases of ischemia and reperfusion, and further explore the relationship between ferroptosis, IRI and Sesn1.
MATERIAL AND METHODS
The hearts of Sprague Dawley (SD) rats undergoing ischemia for varying lengths of time or having undergone ischemia followed by varying lengths of reperfusion were examined. The occurrence of ferroptosis was verified by detecting changes in ferroptosis biomarkers. In addition, ferrstatin-1 (Fer-1) was administered to demonstrate the effect of ferroptosis in myocardial IRI and to detect changes in Sesn1.
RESULTS
The results showed that the myocardial damage was more severe with more prolonged myocardial ischemia. There were no significant changes in ferroptosis biomarkers in cardiac tissues during the ischemia phase, the levels of iron and malondialdehyde (MDA) were elevated, and the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) were decreased after myocardial IRI. Compared to the ischemia/reperfusion (I/R) group, the treatment with Fer-1 before reperfusion can attenuate myocardial IRI, reverse the decrease in GPX4 and FTH1 expression, and decrease the rise in iron content and MDA. In addition, we found that the expression of Sesn1 was reduced in hearts that suffered IRI; however, the treatment with Fer-1 can reverse this situation.
CONCLUSIONS
Ferroptosis occurred during the myocardial reperfusion phase but not ischemia. The inhibition of ferroptosis exerted beneficial effects on myocardial IRI, providing a theoretical basis for targeted therapy in patients with AMI. Sestrin 1, regulated by ferroptosis, may play an important role in myocardial IRI.
Topics: Rats; Animals; Ferroptosis; Myocardial Reperfusion Injury; Rats, Sprague-Dawley; Sestrins; Myocardial Reperfusion; Myocardial Infarction; Coronary Artery Disease; Iron; Biomarkers; Reperfusion Injury
PubMed: 36413176
DOI: 10.17219/acem/153599 -
Circulation Journal : Official Journal... 2016Despite many advances in percutaneous and surgical interventions in the treatment of coronary artery disease (CAD), up to one-third of patients are still either not... (Review)
Review
Despite many advances in percutaneous and surgical interventions in the treatment of coronary artery disease (CAD), up to one-third of patients are still either not candidates or receive suboptimal revascularization. Calpains are a class of calcium-activated non-lysosomal cysteine proteases that serve as a proteolytic unit for cellular homeostasis. Uncontrolled activation of calpain has been found to be involved in the pathogenesis of myocardial reperfusion injury, cardiac hypertrophy, myocardial stunning and cardiac ischemia. Inhibition of calpains has been shown to significantly attenuate myocardial stunning and reduced infarct size after ischemia-reperfusion. Calpain inhibition therefore serves as a potential medical therapy for patients suffering from a number of diseases, including CAD.
Topics: Animals; Calpain; Cardiomegaly; Coronary Artery Disease; Enzyme Activation; Humans; Myocardial Reperfusion Injury
PubMed: 26489456
DOI: 10.1253/circj.CJ-15-0997 -
The Journal of Physiological Sciences :... May 2015Ischemic heart disease is one of the major causes of death worldwide. Ischemia is a condition in which blood flow of the myocardium declines, leading to cardiomyocyte... (Review)
Review
Ischemic heart disease is one of the major causes of death worldwide. Ischemia is a condition in which blood flow of the myocardium declines, leading to cardiomyocyte death. However, reperfusion of ischemic regions decreases the rate of mortality, but it can also cause later complications. In a clinical setting, ischemic heart disease is always coincident with other co-morbidities such as diabetes. The risk of heart disease increases 2-3 times in diabetic patients. Apoptosis is considered to be one of the main pathophysiological mechanisms of myocardial ischemia-reperfusion injury. Diabetes can disrupt the anti-apoptotic intracellular signaling cascades involved in myocardial protection. Therefore, targeting these changes may be an effective cardioprotective approach in the diabetic myocardium against ischemia-reperfusion injury. In this article, we review the interaction of diabetes with the pathophysiology of myocardial ischemia-reperfusion injury, focusing on the contribution of apoptosis in this context, and then discuss the alterations of pro-apoptotic or anti-apoptotic pathways probably responsible for the loss of cardioprotection in diabetes.
Topics: Apoptosis; Diabetes Complications; Humans; Insulin Resistance; Ischemic Postconditioning; Ischemic Preconditioning, Myocardial; KATP Channels; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Models, Cardiovascular; Myocardial Ischemia; Myocardial Reperfusion Injury; Oxidative Stress; Signal Transduction
PubMed: 25726180
DOI: 10.1007/s12576-015-0365-8 -
Current Drug Targets 2015Cardiovascular diseases (CVD) are the leading cause of death, chronic illness and disability in Western countries. The most common cause of CVD derives from the harmful... (Review)
Review
Cardiovascular diseases (CVD) are the leading cause of death, chronic illness and disability in Western countries. The most common cause of CVD derives from the harmful effects of acute myocardial ischemia and subsequent reperfusion injury. Cardioprotection against acute ischemia/ reperfusion injury is made possible by the "conditioning protocols." Conditioning is obtained by applying a few periods of brief ischemia and reperfusion in the event of prolonged (index) ischemia that may cause myocardial infarction. Whilst the conditioning stimulus is applied before the index ischemia in ischemic pre-conditioning, it is applied after the event in post-conditioning. Pre and post- conditioning stimuli can be applied in a different/remote organ (remote pre- and post-conditioning); in this case conditioning stimulus can also be applied during the index event, in the so called remote per-conditioning. All these endogenous cardioprotective strategies recruit endogenous cytoprotective agents and factors that elicit specific cardioprotective pathways. Here, we discuss many of these cardioprotective factors compared to literature and highlight their main characteristics and mechanisms of action. Enphasis is given to endogenous cardioprotective agents acting or not on surface receptors, including chromogranin A derivatives, ghrelin-associated peptides, growth factors and cytokines, and to microvesicles and exosomes. Moreover the cardioprotective effects of gasotransmitters nitric oxide, hydrogen sulphide and carbon monoxide are reviewed. The possible clinical translation of these knowledge for future successful therapies is briefly and critically discussed.
Topics: Animals; Carbon Monoxide; Cardiotonic Agents; Gasotransmitters; Humans; Hydrogen Sulfide; Ischemic Postconditioning; Ischemic Preconditioning, Myocardial; Myocardial Ischemia; Myocardial Reperfusion Injury; Nitric Oxide
PubMed: 25751010
DOI: 10.2174/1389450116666150309115536 -
International Journal of Clinical and... 2015Myocardial infarction (MI) denotes the death of cardiac myocytes due to extended ischemia. Myocardial reperfusion is the restoration of coronary blood flow after a... (Comparative Study)
Comparative Study
Myocardial infarction (MI) denotes the death of cardiac myocytes due to extended ischemia. Myocardial reperfusion is the restoration of coronary blood flow after a period of coronary occlusion. Reperfusion has the potential to salvage ischemic myocardium but paradoxically can cause injury, a phenomenon called as 'reperfusion injury' (IR). Standard histologic, immunohistochemical and Elisa techniques were used to study the histopathologic, oxidative, apoptotic and inflammatory changes in MI and IR. The IL-6 levels in the LV of the MI group were significantly raised as compared to the IR group (P=0.0008). Plasma IL-6 was also significantly increased in the MI group as compared to the IR group (P=0.031). MI model was also associated with increase in the neutrophil polymorphs number in the infarction related myocardium as compared to the re-perfused myocardium. A significant increase in troponin I level in the MI group as compared to the IR group is also seen (P=0.0001). Our IR model showed enhanced pro-apoptotic mediators like cleaved caspase-3 (P=0.005) and cytochrome c in the myocardium as compared to the MI model. In conclusion, myocardial damage in MI is mainly due to ischemic necrosis and inflammatory mechanisms while apoptosis is the main mechanism of cell death in IR in addition to limited ischemic necrosis.
Topics: Animals; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction; Myocardial Reperfusion Injury
PubMed: 26464621
DOI: No ID Found