The Impact of Normobaric Hypoxia and Intermittent Hypoxic Training on Cardiac Biomarkers in Endurance Athletes: A Pilot Study.

This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia has been reported to elicit both beneficial and adverse changes in the cardiovascular system, but its impact on the myocardium during acute exercise and altitude/hypoxic training remains less understood. We aimed to determine how a single bout of intense interval exercise and a four-week period of high-intensity endurance training under normobaric hypoxia affect cardiac marker activity in swimmers. Sixteen young male swimmers were divided into two groups: one undergoing training in hypoxia and the other in normoxia. Cardiac markers, including troponin I and T (cTnI and cTnT), heart-type fatty acid-binding protein (H-FABP), creatine kinase-MB isoenzyme (CK-MB), and myoglobin (Mb), were analyzed to assess the myocardium's response. We found no significant differences in the physiological response of the cardiac muscle to intense physical exertion between hypoxia and normoxia. Four weeks of IHT did not alter the resting levels of cTnT, cTnI, and H-FABP, but it resulted in a noteworthy decrease in the resting concentration of CK-MB, suggesting enhanced cardiac muscle adaptation to exercise. In contrast, a reduction in resting Mb levels was observed in the control group training in normoxia. These findings suggest that IHT at moderate altitudes does not adversely affect cardiac muscle condition and may support cardiac muscle adaptation, affirming the safety and efficacy of IHT as a training method for athletes.

Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging.

BACKGROUND: Aging is a main risk factor for the development of cardiovascular diseases (CVDs). Gallic acid (GA) is a phenolic compound derived from a wide range of fruits. GA has a wide spectrum of pharmacological properties, including anti-oxidative, anti-inflammatory, and cardioprotective effects. This research was conducted to determine the cardioprotective effect of GA on cardiac hypertrophy in aged rats. METHODS AND RESULTS: Following histological evaluation and through observing the heart, we found that GA improved the cardiac hypertrophy induced by D-galactose (D-GAL) in cardiac cells. To clarify the causes for this anti-aging effect, we evaluated the malonic dialdehyde levels and antioxidant enzyme activity in rat cardiac tissue. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in serum were measured. The levels of genes related to mitochondrial biogenesis, mitophagy, and apoptosis in cardiac tissue were surveyed. The findings represented that GA ameliorated antioxidant enzyme activity while significantly decreasing the malonic dialdehyde levels. Real-time PCR analysis proposed that GA effectively improved mitochondrial biogenesis in the heart via regulating the expression levels of Sirtuin 1 (SIRT1), PPARγ coactivator 1α (PGC1-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). GA also mitigated apoptosis in the heart by modulating the expression levels of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X (Bax). In addition, GA improved serum LDH and CK-MB levels. CONCLUSIONS: GA may alleviate aging-induced cardiac hypertrophy via anti-oxidative, mitoprotective, and anti-apoptotic mechanisms.

[Expression and clinical significance of circRNA cSMARCA5 in patients with acute myocardial infarction].

Objective: To investigate the expression level and clinical significance of cSMARCA5 in the patients with acute myocardial infarction (AMI). Methods: This study was a case-control study. A total of 100 patients with AMI and 100 patients without coronary heart disease who received treatment in the Department of Cardiology, Peking University Third Hospital from September to December 2021 were included in the study according to the principle of 1∶1 frequency matching. The expression levels of cSMARCA5 in the peripheral blood of AMI patients and control groups were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The receiver operating characteristic (ROC) curve was used to calculate the diagnostic ability of cSMARCA5 for AMI. Spearman or Pearson correlation analysis was used to explore the correlation between cSMARCA5 and the degree of myocardial necrosis, coronary lesion severity and GRACE risk stratification score. Bioinformatics analysis was used to predict the possible mechanism of cSMARCA5 in pathological changes of AMI. Results: The age [M (Q1,Q3)] of AMI patients and control group was 63.0 (56.0, 71.5) and 63.0 (53.0, 75.5) (P=0.622), and the proportion of males was 75.0% (75 cases) and 46.0% (46 cases) (P<0.001), respectively. The expression level [M (Q1,Q3)] of cSMARCA5 was significantly lower in AMI patients compared with the control group [0.37 (0.22, 0.73) vs 1.03(0.71, 1.75), P<0.001]. ROC analysis showed that the area under the curve of cSMARCA5 in diagnosing AMI was 0.83 (95%CI: 0.77-0.89, P<0.001), with a sensitivity of 89.0% and specificity of 67.7%. cSMARCA5 was negatively correlated with creatine kinase isoenzyme MB (r=-0.203, P=0.041), troponin T (r=-0.230, P=0.023) and N-terminal brain natriuretic peptide precursor (r=-0.250, P=0.012), and positively correlated with left ventricular ejection fraction (r=0.201, P=0.042). In addition, the expression level of cSMARCA5 was negatively correlated with SYNTAX score (r=-0.196, P=0.048) and GRACE risk score (r=-0.321, P=0.001). Bioinformatic analysis suggested that cSMARCA5 might be involved in the process of AMI through regulating the gene expression of tumor necrosis factor. Conclusions: The expression of cSMARCA5 is significantly decreased in peripheral blood of AMI patients compared with control group, and its expression level is negatively correlated with the severity of myocardial infarction. cSMARCA5 is expected to be a potential biomarker of AMI.

Protective Effects and Mechanisms of Melatonin on Stress Myocardial Injury in Rats.

ABSTRACT: Prolonged and intense stress can exceed the body's normal self-regulation and limited compensatory and repair capacity, resulting in pathological damage to the body. In this study, we established a rat stress myocardial injury (SMI) model to explore the protective effect of melatonin (MLT) on SMI and its possible mechanisms of action. Adult female Sprague Dawley (SD) rats were randomly divided into 5 groups: blank control group (NC), SMI group, MLT low-dose group, MLT medium-dose group, and MLT high-dose group, and 10 rats in each group were used to establish a SMI model by the water immersion restraint method. We observed the changes in body weight and tail vein glucose of each group. Serum levels of corticosterone (Cort), creatine kinase isoenzyme (CK-MB), and Troponin Ⅰ (Tn-Ⅰ) and activity of lactic acid dehydrogenase were measured by ELISA. Transcriptome sequencing was used to find differentially expressed genes in the control and model groups, and the results were verified by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). HE staining was used to visualize the pathological changes in the heart tissue of each group, and Western blot was used to study the differences in protein expression in the cardiomyocytes of each group to further corroborate the results. The body weight growth rate of rats in the SMI group was significantly lower than that of the NC group ( P < 0.01), and the body weight growth rate of rats in the MLT high-dose group was significantly higher than that of the SMI group ( P < 0.05) with no significant difference compared with the NC group rats. The mean blood glucose of rats in the SMI group was significantly higher compared with the NC group ( P < 0.001), while the mean blood glucose of rats in the MLT administration groups was dose-dependently reduced compared with the SMI group. By RNA-seq and bioinformatics tools such as KEGG and Gene ontology, we found that the circadian clock-related genes Ciart , Arnt1 , Per1 , and Dbp were significantly downregulated in the SMI group during water immersion stress, and differentially expressed genes were enriched in the p38MAPK signaling pathway and p53 signaling pathway. Moreover, genes related to inflammation and apoptosis were differentially expressed. ELISA results showed that Cort, CK-MB, and Tn-Ⅰ levels were significantly higher in the SMI group compared with the NC group ( P < 0.01) and melatonin reduced the levels of Cort, CK-MB, and Tn-Ⅰ and decreased lactic acid dehydrogenase activity in rat serum. HE staining results showed that melatonin could attenuate stress-generated myocardial injury. Western blot showed that melatonin reduced the expression of p38MAPK, p53, Bax, and caspase-3 and increased the expression of Bcl-2 protein in rat heart. Melatonin can inhibit myocardial injury caused by water immersion, and its mechanism of action may be related to the regulation of the expression of circadian clock genes such as Ciart , Arnt1 , Per1 , and Dbp ; the inhibition of the expression of proapoptotic proteins such as p38MAPK, p53, Bax, and caspase-3; and the increase of the expression of Bcl-2 antiapoptotic protein.

Circulating small extracellular vesicle-encapsulated SEMA5A-IT1 attenuates myocardial ischemia-reperfusion injury after cardiac surgery with cardiopulmonary bypass.

Cardiomyocyte injury is a common complication during cardiac surgery with cardiopulmonary bypass (CPB). Studies have shown that circulating small extracellular vesicles (sEVs) are involved in the pathological process of cardiovascular diseases via delivering signaling molecules. This study aims to investigate the relationship between circulating sEV-encapsulated long noncoding RNAs (lncRNAs) and cardiac injury after CPB. Here, we found that the expression of sEV SEMA5A-IT1 in serum samples of patients after CPB was higher than that of pre-CPB serum samples. Moreover, serum-derived sEV SEMA5A-IT1 levels were negatively correlated with creatine kinase-MB (CK-MB) levels in patients who underwent CPB operation. Notably, circulating sEVs packaged with SEMA5A-IT1 could be uptaken by cardiomyocyte-like cells AC16 and increased SEMA5A-IT1 expression in AC16 cells. Upregulated SEMA5A-IT1 protected cardiomyocytes against hypoxia/reoxygenation injury, confirmed by increased cell viability, reduced cell apoptosis, and inhibited ferroptosis in AC16 cells. Mechanistically, SEMA5A-IT1 regulated the expression of B-cell CLL/lymphoma 2 (BCL2) and solute carrier family 7 member 11 (SLC7A11) through sponging miR-143-3p. Transfection of miR-143-3p mimics, BCL2, or SLC7A11 knockdown could attenuate the protective effect of SEMA5A-IT1 on cardiomyocytes. In conclusion, we propose that SEMA5A-IT1, which is transported to cardiomyocytes through circulating sEVs, is an important regulatory molecule that protects cardiomyocytes from ischemia-reperfusion injury, providing a target for the prevention and treatment of myocardial ischemia-reperfusion injury.

Ischaemic preconditioning-induced serum exosomes protect against myocardial ischaemia/reperfusion injury in rats by activating the PI3K/AKT signalling pathway.

Ischaemia/reperfusion (I/R) injury can lead to severe arrhythmia and aggravate myocardial damage. Exosomes are small-membrane vesicles that play a protective role in myocardial I/R injury. This study aimed to explore the protective effects of ischaemic preconditioning (IPC)-induced serum exosomes (IPC-Exo) on myocardial I/R injury in rats and its underlying mechanism. Serum exosomes were extracted from IPC rats and quantified using a bicinchoninic acid assay kit. IPC-Exo (50 µg) was injected into the infarcted myocardium immediately after ligation. Rats were randomly divided into Sham, I/R, IPC-Exo + I/R, I/R + LY294002, and I/R + IPC-Exo + LY294002 groups. Haemodynamic parameters were measured by physiological recording. Transthoracic echocardiography was used to detect cardiac function. The serum levels of creatine kinase isomer-MB, lactate dehydrogenase, aspartate transaminase, tumour necrosis factor-alpha, interleukin (IL)-1ß, and IL-10 were detected by enzyme-linked immunosorbent assay. Triphenyl tetrazolium chloride staining was used to measure the myocardial infarct size. Apoptosis in myocardial tissues was detected by TUNEL staining. Western blotting was used to detect the levels of PI3K/AKT and apoptosis-related proteins. Our results showed that treatment with IPC-Exo ameliorated cardiac function and reduced inflammatory factor production, cardiomyocyte apoptosis, and myocardial infarct size. Moreover, IPC-Exo treatment promoted the protein expression of Bcl-2, p-PI3K, and p-AKT but inhibited that of caspase-3 and Bax. However, treatment with LY294002 significantly reversed that IPC-Exo-induced increase in p-PI3K and p-AKT levels, improvement of haemodynamics, and decrease of inflammatory factor production and apoptosis in the I/R + IPC-Exo group. Taken together, our results suggest that IPC-Exo may alleviate I/R injury via activating the PI3K/AKT signalling pathway.

Inhibition of inducible nitric oxide synthase protects against the deleterious effects of sub-lethal sepsis and ethanol in the cardiorenal system.

We tested the hypothesis that ethanol would aggravate the deleterious effects of sub-lethal cecal ligation and puncture (SL-CLP) sepsis in the cardiorenal system and that inhibition of inducible nitric oxide synthase (iNOS) would prevent such response. Male C57BL/6 mice were treated with ethanol for 12 weeks. One hour before SL-CLP surgery, mice were treated with N6-(1-iminoethyl)-lysine (L-NIL, 5 mg/kg, i.p.), a selective inhibitor of iNOS. A second dose of L-NIL was administered 24 h after SL-CLP surgery. Mice were killed 48 h post surgery and the blood, the renal cortex, and the left ventricle (LV) were collected for biochemical analysis. L-NIL attenuated the increase in serum creatinine levels induced by ethanol, but not by SL-CLP. Ethanol, but not SL-CLP, increased creatine kinase (CK)-MB activity and L-NIL did not prevent this response. In the renal cortex, L-NIL prevented the redox imbalance induced by ethanol and SL-CLP. Inhibition of iNOS also decreased lipoperoxidation induced by ethanol and SL-CLP in the LV. L-NIL prevented the increase of pro-inflammatory cytokines and reactive oxygen species induced by ethanol and (or) SL-CLP in the cardiorenal system, suggesting that iNOS modulated some of the molecular mechanisms that underlie the deleterious effects of both conditions in the cardiorenal system.

Cardiac Biomarker Abnormalities Are Closely Related to Prognosis in Patients with COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is erupting and spreading globally. Cardiovascular complications secondary to the infection have caught notice. This study aims to delineate the relationship of cardiac biomarkers and outcomes in severe cases of corona virus disease 2019 (COVID-19). One hundred forty-eight critically ill adult patients with COVID-19 were enrolled. From these patients, the demographic data, symptoms, cardiac biomarkers, treatments, and clinical outcomes were collected. Data were compared between survivors and non-survivors. Four patients in the non-survivor group were selected, and their cardiac biomarkers were collected and analyzed. Among the 148 patients, the incidence of cardiovascular complications was 19 (12.8%). Five of them were survivors (5.2%), and 14 of them were non-survivors (26.9%). Compared with the survivors, the non-survivors had higher levels of high-sensitivity cardiac troponin I, creatine kinase isoenzyme-MB, myoglobin, and N-terminal pro-brain natriuretic peptide (P < 0.05). The occurrence of cardiovascular events began at 11-15 days after the onset of the disease and reached a peak at 14-20 days. COVID-19 not only is a respiratory disease but also causes damage to the cardiovascular system. Cardiac biomarkers have the potential for early warning and prognostic evaluation in patients with COVID-19. It is recommended that cardiac biomarker monitoring in patients with COVID-19 should be initiated at least from the 11th day of the disease course.

The Clinical Efficacy of N-Acetylcysteine in the Treatment of ST Segment Elevation Myocardial Infarction.

The aim of this study was to evaluate the clinical efficacy of N-acetylcysteine (NAC) in the treatment of ST segment elevation myocardial infarction (STEMI).PubMed, EMBASE, Cochrane Library, and Web of Science were searched systematically from the establishment of the database to June 2020. Two researchers independently completed literature screening and data extraction and conducted a meta-analysis.Nine articles including 1419 patients were enrolled. Meta-analysis showed that all-cause mortality [RR = 0.56, 95%CI (0.33, 0.93), P = 0.02], occurrence of major adverse cardiovascular events (MACE) [RR = 0.63, 95%CI (0.47, 0.85), P = 0.002], and myocardial enzyme hs-TnT level [SMD = -0.42, 95%CI (-0.71, -0.13), P = 0.005] were significantly lower in patients with STEMI treated with NAC than those in the control group. There was no significant difference between the NAC group and the control group in new congestive heart failure [RR = 0.94, 95%CI (0.48, 1.82), P = 0.84], ejection fraction [MD = 2.00, 95%CI (-0.59, 4.60), P = 0.13], and CK-MB [SMD = -0.18, 95%CI (-0.47, 0.11), P = 0.23]. There was no significant difference in the occurrence of adverse reactions between the NAC group and the control group [RR = 1.04, 95%CI (0.57-1.89), P = 0.90].NAC can reduce the all-cause mortality and MACE cases of STEMI.

Cytoprotective Potential of Aged Garlic Extract (AGE) and Its Active Constituent, S-allyl-l-cysteine, in Presence of Carvedilol during Isoproterenol-Induced Myocardial Disturbance and Metabolic Derangements in Rats.

This study was conducted to determine the potential interaction of aged garlic extract (AGE) with carvedilol (CAR), as well as to investigate the role of S-allyl-l-cysteine (SAC), an active constituent of AGE, in rats with isoproterenol (ISO)-induced myocardial dysfunction. At the end of three weeks of treatment with AGE (2 and 5 mL/kg) or SAC (13.1 and 32.76 mg/kg), either alone or along with CAR (10 mg/kg) in the respective groups of animals, ISO was administered subcutaneously to induce myocardial damage. Myocardial infarction (MI) diagnostic predictor enzymes, lactate dehydrogenase (LDH) and creatinine kinase (CK-MB), were measured in both serum and heart tissue homogenates (HTH). Superoxide dismutase (SOD), catalase, and thiobarbituric acid reactive species (TBARS) were estimated in HTH. When compared with other groups, the combined therapy of high doses of AGE and SAC given alone or together with CAR caused a significant decrease in serum LDH and CK-MB activities. Further, significant rise in the LDH and CK-MB activities in HTH was noticed in the combined groups of AGE and SAC with CAR. It was also observed that both doses of AGE and SAC significantly increased endogenous antioxidants in HTH. Furthermore, histopathological observations corroborated the biochemical findings. The cytoprotective potential of SAC and AGE were dose-dependent, and SAC was more potent than AGE. The protection offered by aged garlic may be attributed to SAC. Overall, the results indicated that a high dose of AGE and its constituent SAC, when combined with carvedilol, has a synergistic effect in preventing morphological and physiological changes in the myocardium during ISO-induced myocardial damage.

Cardioprotective effect of boswellic acids against doxorubicin induced myocardial infarction in rats.

The aim of the present study was to evaluate the cardioprotective activity of boswellic acids in doxorubicin (DOX) induced cardiotoxicity. DOX (2.5mg/kg) was used intraperitoneally in rats to induce cardiotoxicity in six divided doses every alternate day over a period of two weeks. Dexrazoxane (10:1) was used as a standard drug. Boswellic acids (250, 500 and 750 mg/kg) were orally administered to rats for 14 days. After 14 days, rats were sacrificed, and blood was withdrawn through cardiac puncture. The blood lipid profile and cardiac biomarkers including LDH, CK-MB, CPK, SGOT and troponin T were measured. The heart of rats was isolated for histopathological studies. Graphpad Prism was used for statistical analysis. There was a significant increase in the level of cardiac enzymes and complete lipid profile parameters in diseased group as compared to control group. Pre-treatment with boswellic acids decreased level of all the measured parameters and decreased the severity of myocardial damage as supported by histopathological studies. It was concluded that boswellic acids possess cardioprotective potential by lowering cardiac biomarkers and blood lipid profile. Thus, boswellic acids might act as cardioprotective agent against doxorubicin induced cardiotoxicity.

Significance changes in the levels of myocardial enzyme in the child patients with Mycoplasma Pneumoniae Pneumonia.

Mycoplasma is a gram-negative with thin wall bacterium that in humans, Mycoplasma pneumoniae causes pneumonia. This experiment was designed to explore the changes of myocardial enzymes in the mycoplasma pneumoniae pneumonia (MPP) child patients, and analyze the clinical value of these changes, in combination with the relevant indicators, symptoms and signs, in the evaluation of the pneumonia mycoplasma infection. For this aim, a total of 120 child patients with MPP in the acute phase,120 child patients with MPP in the recovery phase and 120 healthy children were simultaneously enrolled into this study to detect the levels of aspartate aminotransferase (AST), creatine kinase (CK), Creatine Kinase Isoenzyme (CK-MB) and lactic dehydrogenase (LDH) in blood. Results showed that MPP patients in the acute phase had higher levels of LDH, CK, CK-MB, AST, PCt, CRP, MPV, PDW, PCt, percentage of neutrophils, WBC count in the peripheral blood and ESR than those of the patients in the recovery patients and healthy children, while the level of PLT was lower (all P<0.05). In the acute phase, the level of CK-MB correlated to the fever, fever duration, extrapulmonary organ damage (except for the myocardial damage) and the antibody titer of MP (all P<0.05). It was concluded that in the acute phase of MMP, the level of CK-MB could not only reflect the myocardial damage readily but also the infection of MP as well as the resultant inflammation and disease progression, which could effectively guide the diagnosis and treatment of MPP.

Protective effects of olmesartan and l-carnitine on doxorubicin-induced cardiotoxicity in rats.

Doxorubicin (DOX), an anthracycline antibiotic, is an important antineoplastic agent due to its high antitumor efficacy in hematological as well as in solid malignancies. The clinical use of DOX is limited due to its cardiotoxic effects. The present study aimed to investigate the possible protective effect of olmesartan (Olm), l-carnitine (L-CA), and their combination in cardiotoxicity induced by DOX in rats. Male albino rats were randomly divided into seven experimental groups (n = 8): group I: normal control, group II: L-CA, group III: Olm, group IV: DOX. The other three groups were treated with Olm (10 mg/kg), L-CA (300 mg/kg), and their combination for 2 weeks after induction of cardiotoxicity by a single dose of DOX (20 mg/kg). In the results, DOX showed a significant elevation in serum troponin I, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) together with increased inflammation manifested by the rise of tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecules-1 (ICAM-1), interleukin IL-1ß (IL-1ß), myeloperoxidase (MPO), nuclear factor-kappa B (NF-κB), and transforming growth factor beta (TGF-ß) in cardiac tissues as well as DOX-induced oxidative stress by increasing in malondialdehyde (MDA) and decreasing in superoxide dismutase (SOD) and glutathione (GSH) in heart tissues. In addition, caspase-3 activity was boosted as indication of increased apoptosis. On the other hand, administration of L-CA and Olm attenuated the DOX-evoked disturbances in the abovementioned parameters. In addition, DOX exhibited echocardiographic changes and severe histopathological changes, which were significantly reversed by L-CA and Olm treatment. In conclusion, the present study data confirm the protective role of L-CA and Olm in DOX-induced cardiotoxicity, which may be related to its antioxidant, antiinflammatory, and antiapoptotic agents.

Inhibition of microRNA-15 protects H9c2 cells against CVB3-induced myocardial injury by targeting NLRX1 to regulate the NLRP3 inflammasome.

BACKGROUND: Viral myocarditis (VMC) is a type of cardiac inflammation that is generally caused by coxsackievirus B3 (CVB3) infection. Several MicroRNAs (miRNAs) are known to play crucial roles in VMC pathogenesis. MiR-15 is reportedly associated with myocardial injury, inflammatory responses and viral infection. Whether miR-15 affects the occurrence and development of VMC remains largely unknown. The roles of miR-15 and their underlying mechanisms in CVB3-stimulated H9c2 cells were assessed in this study. METHODS: We infected H9c2 cells with CVB3 to establish a VMC cellular model. We then determined the effects of miR-15 inhibition on three cardiomyocyte injury markers: lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I). The impact on CVB3-induced cell apoptosis and pro-inflammatory cytokines was also investigated. The effects of miR-15 inhibition on NLRP3 inflammasome activation were also assessed. The target relationship between miR-15 and NOD-like receptor X1 (NLRX1) was determined using a luciferase reporter assay. RESULTS: MiR-15 expression was significantly upregulated in H9c2 cells after CVB3 infection. Inhibition of miR-15 significantly decreased the CVB3-induced levels of LDH, CK-MB and cTn-I. It also elevated cell viability, reduced CVB3-induced cell apoptosis and decreased the generation of the interleukins IL-1ß, IL-6 and IL-18. Furthermore, we determined that miR-15 inhibition suppressed NLRP3 inflammasome activation by downregulating NLRP3 and caspase-1 p20 expression. We found a direct target relationship between miR-15 and NLRX1. Additionally, inhibition of NLRX1 reversed the protective effects of miR-15 inhibition against CVB3-induced myocardial cell injury by regulating the NLRP3 inflammasome. CONCLUSION: Our results indicate that miR-15 inhibition alleviates CVB3-induced myocardial inflammation and cell injury. This may be partially due to NLRX1-mediated NLRP3 inflammasome inactivation.

Downregulation of miR-483-5p decreases hypoxia-induced injury in human cardiomyocytes by targeting MAPK3.

BACKGROUND: MiR-483-5p was recently identified as a risk factor in the early stages of acute myocardial infarction (AMI) patients. Here, we further investigated how miR-483-5p affects cardiomyocyte apoptosis and oxidative stress under hypoxic conditions. METHODS: Plasma samples were collected from AMI patients and healthy volunteers. The expression of miR-483-5p was determined using quantitative real-time PCR. An in vitro hypoxic model was constructed to mimic AMI in AC16 cells. Cell viability, apoptosis and oxidative stress biomarker levels (MDA, SOD and CAT) were respectively determined using CCK-8, flow cytometry and commercial assay kits. RESULTS: The expression levels of miR-483-5p were significantly higher in AMI patients than in control subjects. Circulating levels of miR-483-5p positively correlated with creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) levels. The in vitro experiments showed that the expression levels of miR-483-5p were also upregulated in hypoxia-induced AC16 cell injury. MiR-483-5p overexpression significantly increased hypoxia-induced cardiomyocyte apoptosis and oxidative stress, while knockdown attenuated these effects. Mechanistically, miR-483-5p directly targets MAPK3 in AC16 cells. Furthermore, the protective effects of miR-483-5p knockdown against hypoxia-induced cardiomyocyte injury are partially dependent on MAPK3. CONCLUSIONS: MiR-483-5p, which targets MAPK3, might be a potential therapeutic target for the diagnosis and prevention of hypoxia-induced myocardial injury.

The Implication of Cardiac Injury Score on In-hospital Mortality of Coronavirus Disease 2019.

BACKGROUNDS: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes. METHODS: This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed. RESULTS: A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013). They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis (P = 0.008). CONCLUSION: The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19.

Microplegia in cardiac surgery: Systematic review and meta-analysis.

BACKGROUND: Consensus on the optimum choice of cardioplegia remains elusive. One possibility that has been suggested to have beneficial properties is microplegia, a cardioplegia of reduced crystalloid volume. The aim of this meta-analysis is to comprehensively investigate microplegia against a range of clinical outcomes. METHODS: To identify potential studies, systematic searches were carried out in four databases (eg, Pubmed, EMBASE). The search strategy included the key concepts of "microplegia" OR "mini-cardioplegia" OR "miniplegia" AND "cardiac surgery." This was followed by a meta-analysis investigating: mortality, crystalloid volume; cardiopulmonary bypass time; cross-clamp time; intra-aortic balloon pump use; spontaneous heartbeat recovery; inotropic support; low cardiac output syndrome; myocardial infarction; acute renal failure; atrial fibrillation, reoperation for bleeding; creatine kinase myocardial band (CK-MB); intensive care unit (ICU) time and hospital stay. RESULTS: Eleven studies comprising 5798 participants were analyzed. Microplegia used a lower volume of crystalloids and led to a higher spontaneous return of heartbeat, odds ratio (OR) 4.271 (95% confidence intervals [CIs]: 1.935, 9.423; I2 = 76.57%; P < .001) and a lower requirement for inotropic support, OR: 0.665 (95% CI: 0.47, 0.941; I2 = 3.53%; P = .021). Microplegia was also associated with a lower CK-MB release, mean difference (MD) -6.448 ng/mL (95% CI: -9.386, -3.511; I2 = 0%; P < .001) and a shorter ICU stay, MD: -0.411 days (95% CI: -0.812, -0.009; I2 = 17.65%; P = .045). All other comparisons were nonsignificant. CONCLUSIONS: Microplegia has similar effects to other types of cardioplegia and is beneficial with regard to spontaneous return of heartbeat, inotropic support, ICU stay, and CK-MB release.

Diagnostic role of postmortem CK-MB in cardiac death: a systematic review and meta-analysis.

Biochemical analysis of creatine kinase MB (CK-MB), which is a biomarker of myocardial damage, is used as a potential adjunct test in clinical and forensic medicine. However, there is no previous meta-analysis that summarizes the diagnostic value of postmortem biochemical analysis of CK-MB in cardiac death. The purpose of this study was to perform a systematic literature review and meta-analysis of postmortem CK-MB in cardiac death for forensic work. Six online databases, including PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI), the China Biomedical Literature Database (CBM), and Wanfang Data, were used to search for related studies. The quality of the included literature was assessed according to the Newcastle-Ottawa Quality Assessment Scale (NOS). The meta-analysis was performed by Review Manager version 5.3 software to investigate the diagnostic role of postmortem CK-MB in cardiac death, especially in myocardial infarction. Sixteen pieces of related literature were identified, all of which were considered high quality. The results of the meta-analysis revealed that the postmortem CK-MB level in the pericardial fluid was significantly higher in the cardiac death group with a standard mean difference (SMD) = 0.63, 95% confidence interval (CI) = 0.09~1.17, p = 0.02. This was also the result in the myocardial infarction group (SMD = 0.83, 95% CI = 0.10~1.56, p = 0.03). No significant difference in CK-MB was found in serum for cardiac death (SMD = -0.31, 95% CI = -0.85~0.24, p = 0.27) or myocardial infarction (SMD = -0.10, 95% CI = -0.69~0.49, p = 0.74). The postmortem biochemical analysis of CK-MB in the pericardial fluid can be used as an auxiliary method in the postmortem diagnosis of cardiac death, along with autopsy and histological investigation.

Cardioprotective Effects of Atorvastatin Are Mediated Through PPARγ in Paraquat-Exposed Rats.

BACKGROUND: Paraquat poisoning is one of leading intoxication worldwide without an effective antidote and treatment protocol. Among the other organs, cardiotoxicity of paraquat has been frequently reported. AIM: The protective effects of atorvastatin (STN) on paraquat-induced cardiotoxicity and the role of peroxisome proliferator-activated receptors γ in the mediation of STN effects were investigated. METHODS: Forty-two male Wistar rats were aliquoted into control or test groups. The animals in test groups in addition of paraquat received saline normal (PQ), pioglitazone (PGT), atorvastatin (STN), PGT + STN, PGT + GW9662, and/or STN + GW9662 for 14 days. RESULTS: PGT and STN lowered lipid peroxidation rate, nitric oxide concentration, and activity of myeloperoxidase and CK/MB in the heart. PGT and STN protected from thiol molecules reduction and PQ-induced histopathological injuries. STN regulated the PQ-induced upregulation of COX-II expression in the heart. All STN-related protective effects were reversed by GW9662 as PPARγ antagonist. CONCLUSIONS: These data suggest a cardioprotective effect for STN against the PQ-induced inflammation and oxidative stress. The pharmacologic approach of these findings indicates that STN through PPARγ pathway lowered the PQ-induced cardiotoxicity.

Sacubitril and valsartan protect from experimental myocardial infarction by ameliorating oxidative damage in Wistar rats.

BACKGROUND: Sacubitril (SAC), a neprilysin inhibitor prevent degradation of neprilysin and activate cGMP signaling pathways leading to rise in blood volume concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and bradykinin. OBJECTIVE: The aim of this study was to evaluate the anti-ischemic effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL). RESULT: Biochemical investigation revealed that SAC along with VAL significantly prevented the antioxidant enzymes (SOD, Catalase, GR, GPx, GST, and GSH) degradation and malondialdehyde (MDA) induced by ISO intoxication in Wistar rats. Along with this, cardiac biomarkers (LDH, CK-MB, ALT, AST, and ALP) were also significantly ameliorated by SACand VAL in ISO-treated rats. Concurrently, decreased infarction area (IA)and marked reduction in myofibril damage by SACand VAL further supported its protective benefits in MI. CONCLUSION: Taken together, the results suggest that inhibition of enzyme neprilysin alleviated the ISO induces myocardial damage mediated by its strong antioxidant potential.