Serum Myocardial Enzymes Research Articles

Electroacupuncture Ameliorates Acute Myocardial Ischemic Injury and Long QT Interval in Mice through the α 1A-Adrenergic Receptor: Electrophysiological, Morphological, and Molecular Evidence.

Acute myocardial ischemia (AMI) is a condition caused by a decrease in blood flow to the heart that can sometimes predispose to acquired long QT syndrome (LQTS), thereby resulting in sudden cardiac death. Recent evidence indicates that electroacupuncture (EA) can alleviate MI injury, but its specific mechanism remains unclear. This study was aimed at investigating the efficacy of EA, which utilizes α1A-adrenergic receptors (α1A-AR) in alleviating MI injury as well as the resulting LQTS. The AMI model was established by ligating the left anterior descending arteries (LAD) of both the wild-type and α1A gene-knockout mice and treating them with EA for three consecutive days. A PowerLab 16 physiological recorder was used to collect the electrocardiogram (ECG) while the serum creatine kinase isoenzymes (CK-MB), lactate dehydrogenase (LDH), and norepinephrine (NE) levels in myocardial tissue were determined by using the enzyme-linked immunosorbent assay (ELISA) kit. Moreover, TTC staining was used to observe the myocardial ischemic area, while H&E and TUNEL staining determined the pathological morphology of the myocardium. Quantitative real-time PCR (qRT-PCR) was used to detect the α1A mRNA, and Western blot was used to detect the specific proteins, such as α1A, cleaved caspase-3, Gq, PLC, p-PKCα, and p-hERG. Our results showed that EA could effectively reduce elevated ST-segment, shorten the extended QT interval, and reduce the serum myocardial enzyme content and the degree of pathological injury in wild mice with MI. EA can also decrease the expression of α1A-AR, PLC, p-PKCα, and NE content in myocardial tissues of wild mice, while those of p-hERG increased in ischemic myocardial tissue. These findings suggested that α1A-AR is involved in the development of MI as well as LQTS. Additionally, EA treatment improves the cardiac function and ischemic long QT interval and plays an important role in reducing the hERG inhibition through the α1A-AR-mediated Gq/PLC/PKCα pathway and myocardial apoptosis. Hence, it is suggested that α1A-AR might become a potential target for EA in treating AMI treatment of myocardial ischemia injury and acquired long QT intervals caused by MI.

Exploring the role of ferroptosis in the doxorubicin-induced chronic cardiotoxicity using a murine model

Doxorubicin (DOX) is an effective antitumor drug; however, but its clinical application is seriously limited by the cardiotoxicity induced by its use. Recent studies have found that ferroptosis is an important mechanism underlying DOX-induced cardiotoxicity. However, existing studies are based on DOX-induced acute or subacute cardiotoxicity model. Therefore, we established a murine model of DOX-induced chronic cardiotoxicity using the clinically relevant cumulative dose, to evaluate the potential molecular mechanism underlying ferroptosis of cardiomycocytes. Male C57 mice were received intraperitoneal injections of DOX at a dose of 3 mg/kg body weight, once a week for 12 weeks. We dynamically analysed echocardiographic findings, serum myocardial enzyme levels, haematological indexes and cardiac histopathological changes. The results showed that, after receiving a cumulative DOX dose of 15 mg/kg, the mice developed anaemia and the function and structure of the heart changed significantly with an increase in the cumulative DOX dose. Importantly, with a cumulative DOX dose of 36 mg/kg, iron overload occurred in the heart tissue. Moreover, RNA-sequencing analysis and experimental verification revealed that ferropotosis is the underlying mechanism of DOX-induced chronic cardiotoxicity. Our results showed that DOX inhibits Slc7a11 in system-Xc, resulting in the reduction of GSH synthesis to prevent GPX4 from scavenging lipid peroxides. In addition, DOX induced the occurrence of ferroptosis via down-regulating Nrf2 expression to inhibit HO-1 and GPx4 levels. Our study provides a new perspective for evaluating the pathophysiology of DOX-induced chronic cardiotoxicity in the future, and developing new potential therapeutic strategies for the prevention and treatment of DOX-induced cardiotoxicity.

Effect of Electroacupuncture at Wushu Acupoints of the Cardiopulmonary Meridian on the Autophagy in Rats with Acute Myocardial Ischemia.

Wushu acupoints are the five acupoints distributed below the human elbow and knee joint. They are all located on the same meridian and divided into five categories: Jing, Ying, Shu, Jing, and He. It has been shown that electroacupuncture (EA) at Shenmen point of heart meridian can improve acute myocardial ischemia (AMI) early. However, it is still unclear if all the Wushu acupoints of the heart meridian can improve AMI. Hence, this study emphasizes Wushu acupoints of heart meridian, compares them with Wushu acupoints of lung meridian, and studies the therapeutic effect of EA at Wushu acupoints on AMI and its possible mechanism. It also discusses the specificity of the heart meridian to heart disease. The AMI model is established by ligation of the left anterior descending coronary artery. The detection methods like the physiological recorder, TTC staining, ELISA, and so forth were used to determine the ECG, myocardial infarct size, serum myocardial enzymes, and myocardial tissue-related protein expression in rats. The heart rate (HR) and ST segment along with creatine kinase (CK), creatine kinase isoenzymes (CK-MB), lactate dehydrogenase (LDH), and myocardial infarctions increased after the induction with AMI. Furthermore, the expressions of PINK1 and Parkin protein also showed an increase. However, EA at Wushu acupoints in the heart meridian can reverse the above changes, whereas EA at the lung meridian exhibits limited effect. It is depicted that the heart meridian has a relatively specific relationship with the heart in a diseased state.

Analysis of Cardiac Adverse Reactions Caused by Different Doses of Adriamycin Chemotherapy in Patients with Breast Cancer.

Purpose This paper is aimed at studying the adverse reactions of breast cancer patients after chemotherapy with different doses of adriamycin. Methods 122 breast cancer patients undergoing mastectomy in the Haining Central Hospital from June 2018 to June 2020 were selected as the research objects. Patients were divided into control group and study group according to the different dose of adriamycin given to patients during chemotherapy. Patients in the control group received intravenous drip of adriamycin at 50 mg/m2. Patients in the study group were given intravenous drip at 75 mg/m2. Patients in both the groups started intravenous drip of cyclophosphamide 500 mg/m2 on the first day of chemotherapy, and chemotherapy for 21 days was a cycle. A total of 6 cycles were carried out. Abnormal electrocardiograph (ECG) is compared between the two groups. Myocardial enzyme and oxidative stress indicators were tested, and Doppler ultrasound examination was conducted. Results After chemotherapy, the abnormal rate of ECG in the study group was 56.46%, which was significantly higher than that in the control group (46.67%). After chemotherapy, the indexes of myocardial enzymes and oxidative stress increased, while superoxide dismutase (SOD) decreased significantly, and the differences were statistically significant. At the end of chemotherapy, the differences of serum myocardial enzymes and oxidative stress indexes in the study group were higher than those in the control group. After chemotherapy, there was no significant difference between left ventricular ejection fraction (LVEF) and Sa in the study group and the control group, but Ea in the study group was higher than that in the control group and E/Ea was lower than that in the control group. Conclusion High-dose adriamycin chemotherapy is more likely to cause accumulation of cardiotoxicity, resulting in decreased cardiac function and cardiac injury in breast cancer patients.

Changes of Electrocardiogram and Myocardial Enzymes in Patients with Intracerebral Hemorrhage.

Purpose Cardiac complications are common in patients with spontaneous intracerebral hemorrhage (ICH). The present study is aimed at observing the incidence of cardiac complications after ICH, so as at improving the understanding of the relationship between cardiac complications and ICH. Methods This is a retrospective study on analyzing electrocardiogram (ECG) and serum myocardial enzyme of 208 patients with ICH admitted to a tertiary hospital from 2018 to 2019. For each patient, demographics, medical history, clinical presentation, ECG, serum myocardial enzyme, and head CT on admission were reviewed. Mortality was noted. Results Among the 208 patients, 145 (69.71%) had one or more ECG abnormalities. The top three abnormalities were corrected QT interval (QTc) prolongation 52 (25%), ST depression 48 (23.08%), and T wave inversion 38 (18.27%). One hundred and thirty-nine patients (66.83%) had increased serum levels of at least one kind of myocardial enzyme, which were high-sensitive cardiac troponin T (hs-cTnT) 79 (37.98%), lactic dehydrogenase (LDH) 80 (38.46%), creatine kinase (CK) 57 (27.40%), and creatine kinase-myocardial subfraction (CKMB) 57 (27.40%). The logistic regression analysis showed the following: secondary intraventricular hemorrhage (SIVH) (odds ratio (OR) 5.32; 95% confidence interval (CI) 2.55–11.08; p < 0.001) and hematoma volume > 30 ml (OR 3.81; 95% CI 1.86–7.81; p < 0.001) were independent predictive factors of QTc prolongation; thalamus location (OR 5.79; 95% CI 1.94–17.28; p < 0.05), hematoma volume > 30 ml (OR 24.187; 95% CI 3.14-186.33; p < 0.05), insular involvement (OR 19.08; 95% CI 5.77-63.07; p < 0.001), and SIVH (OR 2.62; 95% CI 1.69-5.86; p < 0.05) were independent predictive factors of ST depression; insular involvement (OR 2.90; 95% CI 1.12–7.50; p < 0.05) and hematoma volume > 30 ml (OR 1.98; 95% CI 1.06–3.70; p < 0.05) were independent predictive factors of increase of CK; Glasgow Coma Scale (GCS) (OR 0.86; 95% CI 0.78–0.98; p < 0.05) and insular involvement (OR 5.56; 95% CI 1.98–15.62; p < 0.05) were independent predictive factors of increase of CKMB; SIVH (OR 2.05; 95% CI 1.07–3.92; p < 0.05) was independent predictive factor of increase of LDH; age (OR 1.03; 95% CI 1.01–1.06; p < 0.05), blood glucose on admission (OR 1.10; 95% CI 1.01–1.20; p < 0.05), and history of antiplatelet drug use (OR 3.50; 95% CI 1.01–12.12; p < 0.05) were independent predictive factors of hs-cTnT. All the injury indexes were not related to in-hospital mortality. Conclusion The study suggests that insular involvement, hematoma volume > 30 ml, and SIVH are the strongest risk factors for ECG abnormalities and elevated myocardial enzymes after ICH followed which are the risk factors such as GCS, age, admission blood glucose, and ICH location in the thalamus.

Effect of Ticagrelor Combined with Acupuncture on Myocardial Infarction and its Effect on Levels of Serum Myocardial Enzymes, Cytokines and T Lymphocytes

To investigate the effect of ticagrelor combined with acupuncture on myocardial infarction and its effect on levels of serum myocardial enzymes, cytokines and T lymphocytes. 90 patients with myocardial infarction were equally divided into observation and control groups. The observation group was treated with ticagrelor combined with acupuncture, while the control group was treated with ticagrelor only. Hemodynamic indexes, left ventricular parameters, serum myocardial enzyme levels, cytokine levels and T lymphocyte levels were analyzed. The incidence of cardiovascular events 1 mo and 3 mo after treatment was investigated. There were no significant differences in heart rate, left ventricular end systolic diameter, left ventricular end diastolic diameter, intermittent septum thickness and posterior wall of left ventricle between two groups (p>0.05), while systolic blood pressure, diastolic blood pressure, mean arterial pressure and left ventricular systolic pressure in the observation group decreased and left ventricular end-diastolic pressure increased (p<0.05). After treatment, the levels of serum myocardial enzymes, tumor necrosis factor alpha, interferon gamma, interleukin-6, interleukin-17, interleukin-21 and interleukin-23 of observation group were significantly lower than control group, while transforming growth factor beta and T lymphocyte levels were significantly higher (p<0.05). The incidences of cardiovascular events in observation group were 2.22 % and 4.44 %, 1 mo and 3 mo after treatment, while it was 4.44 % and 8.89 %, respectively, in control group (p<0.05).

Proteomic Sequencing of Stellate Ganglions in Rabbits With Myocardial Infarction.

The stellate ganglion (SG) of the autonomic nervous system plays important role in cardiovascular diseases (CDs). Myocardial infarction (MI) is associated with sustained increasing cardiac sympathetic nerve activity. Expressions and functions of proteins in SG tissue after MI are remaining unclear. This study is to explore the expression characteristics of proteins in SGs associated with MI. Japanese big-ear white rabbits (n = 22) were randomly assigned to the control group and MI group. The MI model was established by left anterior descending coronary artery ligation and confirmed by serum myocardial enzymes increasing 2,3,5-triphenyltetrazolium (TTC) staining and echocardiography. The expressions of proteins in rabbit SGs after MI were detected using tandem mass tags (TMT) quantitative proteomic sequencing. There were 3,043 credible proteins were predicted in rabbit SG tissues and 383 differentially expressed proteins (DEPs) including 143 upregulated and 240 downregulated proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEPs involved in adrenergic signaling in cardiomyocytes, positive regulation of ERK1 and ERK2 cascade, and other biological processes. Three kinds of proteins directly correlated to CDs were selected to be validated by the subsequent western blot experiment. This study first identified the characterization of proteins in rabbit SG after MI, which laid a solid foundation for revealing the mechanism of roles of SG on the MI process.

Effects of Full Inhalation of Sevoflurane and Total Intravenous Anesthesia on Hemodynamics, Serum Myocardial Enzymes, and Myocardial Markers in Elderly Patients Undergoing Hysterectomy.

Objective To compare the effects of sevoflurane inhalation and intravenous anesthesia on hemodynamics, serum myocardial enzymes, and myocardial markers in elderly patients undergoing hysterectomy. Methods Group A and group B were established randomly regarding a total of 126 elderly patients who underwent an elective hysterectomy. Patients in group A were given full anesthesia with sevoflurane, and patients in group B were given anesthesia with intravenous anesthesia. The operation time, anesthesia time, and recovery time in Postanesthesia Care Unit (PACU) were compared; plasma cortisol concentration, hemodynamics, serum myocardial enzymes, and myocardial markers were detected and compared between the two groups of patients before anesthesia (T0), after anesthesia (T1), and after surgery (T2). Results Group A observed a longer extubation time and recovery time in PACU than group B (P < 0.05). Results show a lower systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and plasma cortisol concentration of T1 by comparison with those of T0 (P < 0.05), but no significant difference remains in terms of intergroup SBP, DBP, and HR (P > 0.05), and there was no interaction effect of groups and time (P > 0.05). The two groups showed no great disparity in the levels of lactate dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), and CK-MB as a subtype of CK before surgery between the two groups of patients (P > 0.05). After surgery, LDH, AST, CK, and CK-MB levels in both groups were witnessed a surge, in which group A obtained higher levels of LDH, AST, CK, and CK-MB (all P < 0.05). Conclusion Total intravenous anesthesia will not increase the hemodynamic fluctuation of elderly patients undergoing hysterectomy and can reduce the damage to the myocardium of patients with surgical trauma, which can protect the myocardium of elderly patients to a certain extent, so it can be adopted as the optimal anesthesia protocol for surgery.

MicroRNA-181b Inhibits Inflammatory Response and Reduces Myocardial Injury in Sepsis by Downregulating HMGB1.

MicroRNAs (miRNAs) are short endogenous noncoding RNAs regulating protein translation. However, the specific mechanism by which miR-181b influences sepsis via high-mobility group box-1 protein (HMGB1) still remains unknown. Thus, the aim of this study is to investigate the mechanism of miR-181b in regulating inflammatory response in sepsis-induced myocardial injury through targeting high-mobility group box-1 protein (HMGB1). Through cecal ligation and puncture (CLP), the rat model of sepsis was established. Then, the effect of altered expression of miR-181b and HMGB1 on cardiomyocytes was investigated. The positive expression rate of HMGB1, concentration of inflammatory factors, and serum myocardial enzyme of myocardial tissues were determined. Besides, the binding site between miR-181b and HMGB1 was determined by bioinformatics information and dual-luciferase reporter gene assay. The expression of related genes in cells of each group was determined by RT-qPCR and western blot analysis, and the apoptosis rate of transfected cells in each group was determined by TUNEL assay. HMGB1 expression and inflammatory factors were significantly increased in myocardial tissue of rats with sepsis. Cell morphology and the infiltration of inflammatory cells were significantly improved by overexpression of miR-181b. miR-181b directly targeted HMGB1, and downregulation of HMGB1 reduced inflammatory factors and myocardial injury and inhibited cardiomyocyte apoptosis in sepsis. This present study suggests that miR-181b decreased inflammatory factors and reduced myocardial injury in sepsis through downregulation of HMGB1. Thus, a better understanding of this process may aid in the development of novel therapeutic agents in sepsis.

Higher Circulating miR-199a-5p Indicates Poor Aerobic Exercise Capacity and Associates With Cardiovascular Dysfunction During Chronic Exposure to High Altitude.

BackgroundHypoxia-induced decline in exercise capacity is ubiquitous among lowlanders who immigrated to high altitudes, which severely reduces their work efficiency and quality of life. Although studies have revealed that hypoxia-induced cardiovascular dysfunction limits exercise capacity at high altitudes, the mechanisms have not been well explored at the molecular level. miR-199a-5p is hypoxia-sensitive and serves as an important regulator in cardiovascular pathophysiology. However, whether miR-199a-5p is involved in cardiovascular dysfunction at high altitudes and contributes to subsequent reductions in exercise capacity remains unknown. Thus, this study aimed at exploring these relationships in a high altitude population.MethodsA total of 175 lowlanders who had immigrated to an altitude of 3,800 m 2 years previously participated in the present study. The level of plasma miR-199a-5p and the concentration of serum myocardial enzymes were detected by qRT-PCR and ELISA, respectively. Indices of cardiovascular function were examined by echocardiography. The exercise capacity was evaluated by Cooper’s 12-min run test and the Harvard Step Test. Furthermore, we explored the biological functions of miR-199a-5p with silico analysis and a biochemical test.ResultsThe level of miR-199a-5p was significantly higher in individuals with poor exercise capacity at 3,800 m, compared with those with good exercise capacity (p < 0.001). miR-199a-5p accurately identified individuals with poor exercise capacity (AUC = 0.752, p < 0.001). The level of miR-199a-5p was positively correlated with cardiovascular dysfunction indices (all, p < 0.001). Furthermore, miR-199a-5p was involved in the oxidative stress process.ConclusionIn this study, we reported for the first time that the level of circulating miR-199a-5p was positively associated with exercise capacity during chronic hypoxia at high altitudes. Moreover, higher miR-199a-5p was involved in hypoxia-induced cardiovascular dysfunctions, thus contributing to poorer exercise endurance at high altitudes.

Study on effects of different habitat processing methods of Salviae Miltiorrhizae Radix et Rhizoma in rats with acute myocardial ischemia

To investigate the effects of different habitat processing methods of Salviae Miltiorrhizae Radix et Rhizoma on acute myocardial ischemia induced by pituitrin in rats. In this experiment, the tail vein injection of pituitrin was used to induce acute myocardial ischemia in rats. Electrocardiograph(ECG) heart rate and ΔST changes were recorded, and the levels of creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH), superoxide dismutase(SOD) and malondialdehyde(MDA) in serum of rats were detected to comprehensively evaluate the effects of six processing methods of Salviae Miltiorrhizae Radix et Rhizoma on serum biochemical indexes of rats with acute myocardial injury. The ECG results showed that the Salviae Miltiorrhizae Radix et Rhizoma dried in a drying oven had a good effect on the improvement of heart rate and ΔST of electrocardiogram after ischemia, and all the other groups had some protective effects to different degrees. The results of biochemical indexes in serum of each group after ischemia showed that the activity of CK-MB decreased most significantly in Salviae Miltiorrhizae Radix et Rhizoma high-dose group with drying in a drying oven after sweating and losing weight in a drying oven, high-dose group with drying in the shade and low-dose group with drying in the shade. The activity of LDH decreased most significantly in Salviae Miltiorrhizae Radix et Rhizoma high-dose group with drying in the shade and low-dose group of drying in the shade. The activity of SOD increased most significantly in Salviae Miltiorrhizae Radix et Rhizoma low-dose group with drying in sun, low-dose group with drying in sun after sweating and losing weight in sun, and low-dose group with drying in a drying oven. The activity of MDA decreased most significantly in Salviae Miltiorrhizae Radix et Rhizoma low-dose group with drying in sun. The comprehensive scoring results showed that the highest score was obtained in Salviae Miltiorrhizae Radix et Rhizoma high-dose group with drying in the shade while the scores of other treatment groups were higher than that of the model group. It could be seen that the Salviae Miltiorrhizae Radix et Rhizoma dried in a drying oven had a good improvement effect on electrocardiograph indexes after acute myocardial injury, the Salviae Miltiorrhizae Radix et Rhizoma dried in the shade had a good improvement effect on serum myocardial enzymes after acute myocardial injury, and the other processing methods had a certain protective effect on myocardial injury. The six processing methods evaluated by pharmacodynamics showed that the Salviae Miltiorrhizae Radix et Rhizoma dried in the shade and dried in a drying oven had good efficacy.

Clinical and Preclinical Systematic Review of Astragalus Membranaceus for Viral Myocarditis.

Astragalus membranaceus (AM) is a traditional Chinese medicine, which possesses a variety of biological activities in the cardiovascular systems. We conducted a clinical and preclinical systematic review of 28 randomized clinical control studies with 2522 participants and 16 animal studies with 634 animals to evaluate the efficacy, safety, and possible mechanisms of AM for viral myocarditis (VM). The search strategies were performed in 7 databases from inception to January 2020. Application of the Cochrane Collaboration's tool 7-item checklist, SYRCLE's tool 10-item checklist, and Rev-Man 5.3 software to analyze the risk of bias of studies and data. The results show the score of clinical study quality ranged from 3 to 7 points with an average of 3.32, and the score of animal study quality ranged from 2 to 5 points with an average of 3. In clinical study, AM significantly reduced serum myocardial enzymes and cardiac troponin I levels and improved the clinical treatment efficiency in VM patients compared with the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions (P > 0.05). Significant increase of the survival rate and decrease of the cardiac cardiology score, cardiac enzymes, and cardiac troponin I were compared with the placebo group in animal studies (P < 0.05). The possible mechanisms of AM are largely through antivirus and antivirus receptors, anti-inflammatory, antioxidation, antiapoptotic, antifibrosis, and reducing cardiac calcium load. In conclusion, the findings suggested that AM is a cardioprotection candidate drug for VM.

Effects of long-term hydrogen intervention on the physiological function of rats

The potential therapeutic effects of molecular hydrogen (H2) have now been confirmed in various human and animal-disease models. However, the effects of H2 on the physiological function in a normal state have been largely neglected. Hydrogen-rich water (HRW) intake and hydrogen inhalation (HI) are the most common used methods for hydrogen administration, the difference in the effects between HRW intake and HI remains elusive. In the present study, the body weight and 13 serum biochemical parameters were monitored during the six-month hydrogen intervention, all these parameters were significantly altered by oral intake of HRW or HI. Among the 13 parameters, the most striking alterations induced by hydrogen treatment were observed in serum myocardial enzymes spectrum. The results also showed that the changes in these parameters occurred at different time points, and the alterations in most of the parameters were much more significant in HI than HRW. The results of this study provides the basic data for the mechanism research and application of molecular hydrogen in the future.

Ethanol Extract of Chinese Hawthorn (Crataegus pinnatifida) Fruit Reduces Inflammation and Oxidative Stress in Rats with Doxorubicin-Induced Chronic Heart Failure.

BackgroundChinese hawthorn (Crataegus pinnatifida) fruit is a traditional Chinese medicine for treatment of digestive system and cardiovascular diseases. The fruit contains polyphenol compounds, such as epicatechin, that have anti-inflammatory activity. This study aimed to investigate the effects of an alcohol extract of hawthorn fruit (HAE) on inflammation and oxidative stress in rats with doxorubicin-induced chronic heart failure (CHF).Material/MethodsRats were intraperitoneally injected with doxorubicin to induce CHF and subsequently treated with HAE intragastrically once daily for 6 weeks. At the end of the experiment, echocardiographic and hemodynamic parameters were assessed, and enzyme-linked immunoassays were used to detect the levels of cardiac injury markers (brain natriuretic peptide, creatine kinase-MB, aspartate aminotransferase, lactate dehydrogenase, copeptin, and adrenomedullin), oxidative stress markers (glutathione peroxidase and malondialdehyde), and inflammatory cytokines (interleukin [IL]-6, IL-8, IL-1β, and tumor necrosis factor-α). The IL-1β, IL-6, glutathione peroxidase-1, and catalase mRNA levels were also measured by quantitative real-time polymerase chain reaction.ResultsOur findings indicated that HAE exerts a cardioprotective effect, as shown by improved echocardiographic and hemodynamic parameters, decreased activity of serum myocardial enzymes, reduced serum levels of CHF markers, and inhibited inflammatory response in cardiac tissue. In addition, HAE treatment downregulated the mRNA expression of IL-1β and tumor necrosis factor-α and upregulated the mRNA expression of glutathione peroxidase-1 and catalase compared with untreated doxorubicin-induced CHF rats.ConclusionsHAE shows promise for the prevention and treatment of CHF. The cardioprotective effect of HAE appears to be related to inhibition of both the inflammatory response and oxidative stress in vivo.

Curcumin suppresses doxorubicin-induced cardiomyocyte pyroptosis via a PI3K/Akt/mTOR-dependent manner.

Doxorubicin (DOX) is one of the most effective anti-neoplastic drugs although its clinical use is limited by the severe cardiotoxicity. Apoptosis and defective autophagy are believed to contribute to DOX-induced cardiotoxicity. Here we explored the effect of curcumin (Cur) on DOX-induced cardiac injury and the mechanism involved with a focus on oxidative stress, autophagy and pyroptosis. Kunming mice were challenged with DOX (3 mg·kg-1, i.p. every other day) with cohorts of mice receiving Cur at 50, 100, 200 and 400 mg·kg-1 via gavage daily. Serum levels of cardiac enzymes, such as aspartate amino transferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and heart homogenate oxidative stress markers, such as superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Echocardiographic and cardiac contraction were examined. Apoptosis, pyroptosis, autophagy and Akt/mTOR-signalling proteins were detected using western blot or electron microscopy. Cardiac contractile properties were assessed including peak shortening, maximal velocity of shortening/relengthening (± dL/dt), time-to-PS, and time-to-90% relengthening (TR90). Superoxide levels were evaluated using DHE staining. GFP-LC3 was conducted to measure autophagosomes. Our study showed that Cur protected against cardiotoxicity manifested by a significant decrease in serum myocardial enzymes and improvement of anti-oxidative capacity. Cur inhibited autophagy and offered overt benefit for cardiomyocyte survive against DOX-induced toxicity. Cur attenuated DOX-induced cardiomyocyte pyroptosis as evidenced by NLR family pyrin domain containing 3 (NLRP3), Caspase-1, and interleukin-18 levels. DOX impaired cardiac function (reduced fractional shortening, ejection fraction, increased plasma cTnI level and TR90, decreased PS and ± dL/dt), the effects of which were overtly reconciled by 100 mg·kg-1 but not 50 mg·kg-1 Cur. H9c2 cells exposure to DOX displayed increased intracellular reactive oxygen species (ROS) and autophagy, the effects of which were nullified by Cur. Autophagy activator rapamycin cancelled off Cur-induced protective effects. Our finding suggested that Cur rescued against DOX-induced cardiac injury probably through regulation of autophagy and pyroptosis in a mTOR-dependent manner.

RP105 plays a cardioprotective role in myocardial ischemia reperfusion injury by regulating the Toll‑like receptor 2/4 signaling pathways.

The revascularization of blood vessels after myocardial infarction can lead to serious myocardial damage. Previous studies showed that radioprotective 105 kDa protein (RP105) is a specific negative regulator of myocardial ischemia reperfusion injury (MIRI). RP105 can modulate the Toll-like receptor (TLR)2/TLR4 signaling pathways. However, the synergistic effect of TLR2/4 regulated by RP105 during MIRI requires further investigation. To determine this effect, a MIRI model was established in rats in the present study. The expression of RP105 was depleted by transfecting RP105-siRNA and then detected using western blotting. Furthermore, the myocardium tissue was stained with the hematoxylin and eosin staining. Knockdown of RP105 promoted the activity of serum myocardial enzymes during MIRI and increased myocardial infarction. The present results indicated that knockdown of RP105 activated the TLR2/4 signaling pathway by modulating the myeloid differentiation primary response 88 and NF-κB signaling pathways. Furthermore, decreased expression of RP105 promoted myocardial cell apoptosis, which induced the damage of myocardial ischemic reperfusion. The present results suggested both TLR2 and TLR4 as key targets of RP105, thus RP105 may be a promising candidate to facilitate the development of novel therapeutic strategies for MIRI.

The circular RNA TLK1 exacerbates myocardial ischemia/reperfusion injury via targeting miR-214/RIPK1 through TNF signaling pathway

PurposeMyocardial ischemia/reperfusion injury (IRI) induces cardiomyocytes death and leads to loss of cardiac function. Circular RNAs (circRNA) have gain increasing interests in modulating myocardial IRI. In this study, we aim to investigate the role and exact mechanism of circTLK1 in the pathogenesis of myocardial IRI. MethodsMyocardial IRI was developed in mice with measuring hemodynamic parameters and the activity of serum myocardial enzymes to evaluate cardiac function. HE and TTC staining were performed to assess infarct area. Expression patterns of circTLK1 and miR-214 were investigated using qRT-PCR assay. Gene expression of circTLK1, miR-214 or RIPK was altered by transfecting with their overexpression or knockdown vectors. The apoptosis of cardimyocytes was assessed by TUNEL staining and Caspase-3 activity analysis. Apoptosis-related markers Bcl-2, Bax, and caspase3, as well as TNF-α signals were determined by western blotting. The interactions of circTLK1/miR-214 and miR-214/RIPK1 were verified using luciferase reporter assay. RNA immunoprecipitation (RIP) was subjected to further definite the direct binding of circTLK1/miR-214. The regulatory network of circTLK1/miR-214/RIPK1 was further validated in vivo. ResultscircTLK1 was an up-regulated circRNA found in a myocardial IRI mouse model. Mice with silencing circTLK1 significantly alleviated the impaired cardiac function indexes and decreased infarct area, thus attenuating the pathogenesis of myocardial IRI. Knockdown of circTLK1 dramatically decreased cardiomyocytes apoptosis, which was determined by apoptosis-related proteins. miR-214 was identified as a downstream effector to reverse circTLK1-mediated damage effects in myocardial IRI. miR-214 could directly target RIPK1 via binding to its' 3′-UTR. Overexpression of RIPK1 led to impaired cardiac function indexes, increased infarct area, and cell apoptosis, which abolished the protective effects of miR-214. The TNF signaling pathway was demonstrated to be involved in the circTLK1/miR-214/RIPK1 regulatory network in myocardial IRI. ConclusionTaken together, our study revealed an up-regulated circRNA, circTLK1, could exacerbate myocardial IRI via targeting miR-214/RIPK1-mediated TNF signaling pathway, which may provide therapeutic targets for treatment.

MicroRNA‑132 promotes oxidative stress‑induced pyroptosis bytargeting sirtuin 1 in myocardial ischaemia‑reperfusion injury.

The present study aimed to investigate the roles of miR‑132 in myocardial ischaemia/reperfusion (I/R) injury and the underlying mechanisms. The myocardial I/R model was established using C57BL/J6mice. Haematoxylin and eosin staining was performed to observe the injury of myocardial tissues. Commercial kits were used to measure the levels of serum myocardial enzymes and inflammatory factors. The invitro I/R model was established by the hypoxia/reoxygenation method using H9C2 cells. A dual luciferase reporter assay was used to confirm the binding of miR‑132 and sirtuin1 (SIRT1). Cell pyroptosis was determined using flow cytometry. Reverse transcription‑quantitative PCR was performed to determine the expression of miR‑132, SIRT1 and inflammatory factors. The levels of peroxisome proliferator‑activated receptor gamma coactivator (PGC)‑1α/nuclear factor erythroid‑2‑related factor 2 (Nrf2) signalling, oxidative stress and pyroptosis‑related proteins were detected by western blotting. Apparent histologic injury and elevated levels of serum myocardial enzymes and inflammatory factors were observed in the myocardial I/R model. miR‑132 was significantly upregulated and SIRT1 was markedly downregulated in I/R myocardial tissues. miR‑132 directly targeted SIRT1 and negatively regulated the expression of SIRT1. PGC‑1α, Nrf2, endothelial nitric oxide synthase and superoxide dismutase levels were significantly decreased, while inducible nitric oxide synthase and malondialdehyde levels were significantly increased by I/R induction. The pyroptosis‑related proteins NLRP3, caspase‑1 and interleukin (IL)‑1β were also significantly elevated by I/R induction. Inhibition of miR‑132 activated PGC‑1α/Nrf2 signalling and inhibited oxidative stress and the expression of the pyroptosis‑related proteins NLRP3, caspase‑1 and IL‑1β, which were all reversed by inhibiting SIRT1 with EX527. The findings of the present study indicated that inhibition of miR‑132 may ameliorate myocardial I/R injury by inhibiting oxidative stress and pyroptosis through activation of PGC‑1α/Nrf2 signalling by targeting SIRT1.

MiR-328 inhibits cell apoptosis and improves cardiac function in rats with myocardial ischemia-reperfusion injury through MEK-ERK signaling pathway.

To explore the influences of micro ribonucleic acid (miR)-328 on rats with myocardial ischemia-reperfusion (IR) injury through the methyl ethyl ketone (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. A total of 36 Sprague-Dawley rats were randomly assigned into the sham group (n=12), model group (n=12), and miR-328 group (n=12). The model of myocardial IR injury was established by ligating the left anterior descending coronary artery, without any intervention in the model group, while 200 μL of miR-328 antagomir was intravenously injected before modeling in the miR-328 group. The activity of the serum myocardial enzymes lactate dehydrogenase (LDH) and creatine kinase-muscle/brain (CK-MB) was determined via ELISA to assess the cardiac function in the three groups of rats, and the mRNA expression level of miR-328 in myocardial tissues was measured through real-time fluorescence qRT-PCR in the sham group, model group, and miR-328 group. TUNEL staining was performed to detect apoptotic cells, and the levels of myocardial apoptosis-associated protein Caspase-3 and phosphorylated MEK1/2 (p-MEK1/2) and p-ERK1/2 proteins were determined using Western blotting. Compared with the sham group, the model group exhibited increased activity of LDH and CK-MB, miR-328 expression level, apoptotic cells, the relative expression level of Caspase-3, and protein levels of p-MEK and p-ERK, with statistically significant differences (p<0.05). Besides, in comparison with the model group, miR-328 group showed a decreased activity of LDH and CK-MB, miR-328 expression level, the relative expression level of Caspase-3, and protein levels of p-MEK and p-ERK, displaying statistically significant differences (p<0.05). MiR-328 modulates the MEK-ERK signaling pathway to inhibit cell apoptosis and improve the cardiac function in rats with myocardial IR injury.

MiR-25 exerts cardioprotective effect in a rat model of myocardial ischemia-reperfusion injury by targeting high-mobility group box 1.

We previously confirmed the targeting of high-mobility group box 1 (HMGB1) by miR-25. This project aims to further investigate whether miR-25 improves myocardial ischemia-reperfusion injury (IRI) in vivo by targeting HMGB1. A rat model of myocardial IRI was established by the ligation of the left anterior descending coronary artery for 45 minutes followed by 2, 4, or 6 hours reperfusion. The expression of miR-25, HMGB1, and apoptosis-related proteins in the myocardium was determined by quantitative real-time polymerase chain reaction (PCR) and western blotting. The activities of myocardial enzymes and the release of inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay. Evans blue/triphenyltetrazolium chloride double staining was performed to assess infarct size. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. MiR-25 expression was significantly downregulated, while HMGB1 was highly expressed at the mRNA and protein levels in myocardial tissues after induction of the IRI model. MiR-25 agomir administration suppressed the expression of HMGB1 in myocardial tissues. Furthermore, administration of both miR-25 agomir and lentivirus-mediated short hairpin RNA (shRNA) interference targeting HMGB1 sh-HMGB1 resulted in reduced serum myocardial enzyme activities, cytokine secretion, and myocardial apoptosis during myocardial IRI. MiR-25 mitigated myocardial IRI-induced damage by targeting HMGB1.