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Arquivos Brasileiros de Cardiologia Apr 2021Myocardial reperfusion is a fundamental part of the treatment for ST elevation myocardial infarction (STEMI) and is responsible for reducing morbidity and mortality in...
BACKGROUND
Myocardial reperfusion is a fundamental part of the treatment for ST elevation myocardial infarction (STEMI) and is responsible for reducing morbidity and mortality in affected patients. However, reperfusion rates are usually lower and mortality rates higher in women compared to men.
OBJECTIVES
To evaluate the prevalence of the use of reperfusion therapies among women and men with STEMI in hospitals where percutaneous coronary intervention (PCI) is available in the state of Sergipe.
METHODS
This is a cross-sectional study that used data from the VICTIM Register. Patients diagnosed with STEMI admitted to the four hospitals (one public and three private) where PCI is available in the state of Sergipe were evaluated, from December 2014 to June 2018. A multivariate analysis with adjusted model using mortality as a dependent variable was made. In all analyses, the level of significance adopted was 5% (p < 0.05).
RESULTS
A total of 878 volunteers with a confirmed diagnosis of STEMI, of which 33.4% were women, were included in the study. Only 53.3% of the patients underwent myocardial reperfusion (134 women versus 334 men). Fibrinolysis was performed only in 2.3% of all patients (1.7% of women versus 2.6% of men; p = 0.422). The rate of primary PCI was lower (44% versus 54.5%; p = 0.003) and hospital mortality was higher (16.1% versus 6.7%; p < 0.001) in women than in men.
CONCLUSION
Women have significantly lower rates of primary PCI and higher hospital mortality. Reperfusion rates were low in both sexes and there was a clear underutilization of thrombolytic agents.
Topics: Brazil; Cross-Sectional Studies; Female; Hospital Mortality; Humans; Male; Myocardial Reperfusion; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Thrombolytic Therapy; Treatment Outcome
PubMed: 33886713
DOI: 10.36660/abc.20190468 -
Disease Markers 2021Myocardial ischemia-reperfusion (I/R) injury (MIRI) refers to the more serious myocardial injury after blood flow recovery, which seriously affects the prognosis of...
OBJECTIVE
Myocardial ischemia-reperfusion (I/R) injury (MIRI) refers to the more serious myocardial injury after blood flow recovery, which seriously affects the prognosis of patients with ischemic cardiomyopathy. This study explored the new targets for MIRI treatment by investigating the effects of miR-190-5p and its downstream target on the structure and function of myocardial cells.
METHODS
We injected agomir miR-190-5p into the tail vein of rats to increase the expression of miR-190-5p in rat myocardial cells and made an I/R rat model by coronary artery occlusion. We used 2,3,5-triphenyl tetrazolium chloride staining, lactate dehydrogenase (LDH) detection, echocardiography, and hematoxylin-eosin (HE) staining to determine the degree of myocardial injury in I/R rats. In addition, we detected the expression of inflammatory factors and apoptosis-related molecules in rat serum and myocardial tissue to determine the level of inflammation and apoptosis in rat myocardium. Finally, we determined the downstream target of miR-190-5p by Targetscan system and dual luciferase reporter assay.
RESULTS
The expression of miR-190-5p in an I/R rat myocardium was significantly lower than that in normal rats. After treatment of I/R rats with agomir miR-190-5p, the ischemic area of rat myocardium and the concentration of LDH decreased. The results of echocardiography and HE staining also found that overexpression of miR-190-5p improved the structure and function of rat myocardium. miR-190-5p was also found to improve the viability of H9c2 cells and reduce the level of apoptosis of H9c2 cells. The results of Targetscan system and dual luciferase reporter assay found that miR-190-5p targeted to inhibit pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1). In addition, inhibition of PHLPP1 was found to improve the viability of H9c2 cells.
CONCLUSION
Therefore, miR-190-5p can reduce the inflammation and apoptosis of myocardium by targeting PHLPP1, thereby alleviating MIRI.
Topics: Animals; Apoptosis; Cell Line; Disease Models, Animal; Echocardiography; Inflammation Mediators; L-Lactate Dehydrogenase; Male; MicroRNAs; Myocardial Reperfusion Injury; Myocardium; Nuclear Proteins; Rats; Rats, Sprague-Dawley
PubMed: 34868398
DOI: 10.1155/2021/8709298 -
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 -
Journal of Cellular and Molecular... Apr 2020Acute myocardial infarction causes lethal injury to cardiomyocytes during both ischaemia and reperfusion (IR). It is important to define the precise mechanisms by which... (Review)
Review
Acute myocardial infarction causes lethal injury to cardiomyocytes during both ischaemia and reperfusion (IR). It is important to define the precise mechanisms by which they die in order to develop strategies to protect the heart from IR injury. Necrosis is known to play a major role in myocardial IR injury. There is also evidence for significant myocardial death by other pathways such as apoptosis, although this has been challenged. Mitochondria play a central role in both of these pathways of cell death, as either a causal mechanism is the case of mitochondrial permeability transition leading to necrosis, or as part of the signalling pathway in mitochondrial cytochrome c release and apoptosis. Autophagy may impact this process by removing dysfunctional proteins or even entire mitochondria through a process called mitophagy. More recently, roles for other programmed mechanisms of cell death such as necroptosis and pyroptosis have been described, and inhibitors of these pathways have been shown to be cardioprotective. In this review, we discuss both mitochondrial and mitochondrial-independent pathways of the major modes of cell death, their role in IR injury and their potential to be targeted as part of a cardioprotective strategy. This article is part of a special Issue entitled 'Mitochondria as targets of acute cardioprotection' and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.
Topics: Apoptosis; Autophagy; Cell Death; Humans; Mitochondria; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Necrosis; Signal Transduction
PubMed: 32155321
DOI: 10.1111/jcmm.15127 -
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 -
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 -
BioMed Research International 2021This study is aimed at investigating the therapeutic effects of tetrandrine (Tet) on myocardial ischemia reperfusion (I/R) injury and probe into underlying molecular...
OBJECTIVE
This study is aimed at investigating the therapeutic effects of tetrandrine (Tet) on myocardial ischemia reperfusion (I/R) injury and probe into underlying molecular mechanism.
METHODS
H9C2 cells were divided into hypoxia/oxygenation (H/R) group, H/R+Tet group, H/R+Tet+negative control (NC) group, and H/R+Tet+miR-202-5p inhibitor group. RT-qPCR was utilized to monitor miR-202-5p and TRPV2 expression, and TRPV2 protein expression was detected via western blot and immunohistochemistry in H9C2 cells. Cardiomyocyte apoptosis was evaluated through detection of apoptosis-related markers and flow cytometry. Furthermore, myocardial enzyme levels were detected by ELISA. Rats were randomly separated into sham operation group, I/R group, I/R+Tet group (50 mg/kg), I/R+Tet+NC group, and I/R+Tet+miR-202-5p inhibitor group. miR-202-5p and TRPV2 mRNA expression was assessed by RT-qPCR. TRPV2 protein expression was detected through western blot and immunohistochemistry in myocardial tissues. Apoptotic levels were assessed via apoptosis-related proteins and TUNEL. Pathological changes were observed by H&E staining. Myocardial infarction size was examined by Evans blue-TCC staining.
RESULTS
Abnormally expressed miR-202-5p as well as TRPV2 was found in H/R H9C2 cells and myocardial tissues of I/R rats, which was ameliorated following Tet treatment. Tet treatment significantly suppressed H/R- or I/R-induced cardiomyocyte apoptosis. ELISA results showed that CK-MB and LDH levels were lowered by Tet treatment in H/R H9C2 cells and serum of I/R rats. H&E staining indicated that Tet reduced myocardial injury in I/R rats. Also, myocardial infarction size was lowered by Tet treatment. The treatment effects of Tet were altered following cotreatment with miR-202-5p inhibitor.
CONCLUSION
Our findings revealed that Tet may ameliorate myocardial I/R damage via targeting the miR-202-5p/TRPV2 axis.
Topics: Animals; Benzylisoquinolines; Cell Line; Gene Expression Regulation; Male; MicroRNAs; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; TRPV Cation Channels
PubMed: 33763489
DOI: 10.1155/2021/8870674 -
Analytical Cellular Pathology... 2023Early reperfusion into the myocardium after ischemia causes myocardial ischemia-reperfusion (I/R) injury and ferroptosis was involved. Ischemia activates the expression...
Early reperfusion into the myocardium after ischemia causes myocardial ischemia-reperfusion (I/R) injury and ferroptosis was involved. Ischemia activates the expression of a series of oxidative stress genes and their downstream regulatory genes, including ferroptosis-related genes such as nuclear factor E2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and SLC7A11. This study adopted primary cardiomyocytes and I/R in rats to evaluate the ferroptosis and changing of Nrf2-SLC7A11/heme oxygenase-1 (HO-1) and . Online analysis tools were used to predict the possible target Kelch-like ECH-associated protein 1 (Keap1) of miR-432-5p. The mimic of miR-432-5p plasmid was constructed to verify the effect of miR-432-5p on ferroptosis. We found that hypoxia/reoxygenation (H/R) in cardiomyocytes and I/R in rats induced lipid peroxidation and ferroptosis in cardiomyocytes. The activation of the Nrf2-SLC7A11/HO-1 pathway protects cardiomyocytes from ferroptosis. Downregulation of miR-432-5p has been confirmed in H/R cardiomyocytes () and cardiomyocytes in myocardial infarction rats (). Upregulation of miR-432-5p inhibited ferroptosis of cardiomyocytes induced by RAS-selective lethal 3 (RSL3), an inhibitor of GPX4 and ferroptosis inducer through decreasing the binding protein of Nrf2, Keap1, which was confirmed by bioinformatics and mutation assay. Knockdown Nrf2 attenuates the protection effect of miR-432-5p on H/R cardiomyocytes. Intravenous delivery of liposome carriers of miR-432-5p remarkably ameliorated cardiomyocyte impairment in the I/R animal model. In conclusion, miR-432-5p inhibits the ferroptosis in cardiomyocytes induced by H/R by activating Nrf2/SLC7A11 axis by degrading Keap1 and is a potential drug target for clinical myocardial infarction treatment.
Topics: Animals; Rats; Ferroptosis; Hypoxia; Ischemia; Kelch-Like ECH-Associated Protein 1; MicroRNAs; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; NF-E2-Related Factor 2
PubMed: 37822721
DOI: 10.1155/2023/1293200 -
International Journal of Molecular... Apr 2020Metabolic syndrome, diabetes, and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is... (Review)
Review
Metabolic syndrome, diabetes, and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. In addition, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.
Topics: Animals; Diabetes Mellitus; Diabetic Cardiomyopathies; Disease Management; Disease Susceptibility; Exercise; Humans; Ischemic Preconditioning; Metabolic Networks and Pathways; Myocardial Ischemia; Myocardial Reperfusion Injury
PubMed: 32326182
DOI: 10.3390/ijms21082896 -
Anastatin Derivatives Alleviate Myocardial Ischemia-Reperfusion Injury via Antioxidative Properties.Molecules (Basel, Switzerland) Aug 2021(±)-Anastatins A and B are flavonoids isolated from . In a previous study, twenty-four di- and tri-substituted novel derivatives of anastatins were designed and their...
(±)-Anastatins A and B are flavonoids isolated from . In a previous study, twenty-four di- and tri-substituted novel derivatives of anastatins were designed and their preliminary antioxidant activities were evaluated. In the present study, the protective effect of myocardial ischemia-reperfusion (I/R) and the systematic antioxidant capacity of 24 derivatives were further studied. Compound was the most potent among all the compounds studied, which increased the survival of H9c2 cells to 80.82%. The antioxidant capability of compound was evaluated in ferric reducing antioxidant power, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, and 2,2-diphenyl-1-picrylhydrazyl assays. It was observed that compound significantly reduced infarcted areas and improved histopathological and electrocardiogram changes in rats with myocardial I/R injury. Moreover, compound decreased the leakage rates of serum lactate dehydrogenase, creatine kinase, and malonyldialdehyde from rat myocardial tissues and increased the level of glutathione and superoxide dismutase activities following myocardial I/R injury in rats. Taken together, we concluded that compound had potent cardioprotective effects against myocardial I/R injury both in vitro and in vivo owing to its extensive antioxidant activities.
Topics: Animals; Antioxidants; Apoptosis; Cell Survival; Flavonoids; Glutathione; Male; Malondialdehyde; Myocardial Reperfusion Injury; Oxidative Stress; Rats
PubMed: 34443365
DOI: 10.3390/molecules26164779