Treatment Of Myocardial Injury Research Articles

Potential Efficacy of Syringaresinol in the Treatment of Myocardial Injury: Inhibition of Pyroptosis and Oxidative Stress

This paper aims to investigate the possible effects of Syringaresinol on a myocardial ischemia/reperfusion injury cell model and uncover the underlying mechanism. A myocardial ischemia/reperfusion injury cell model was constructed using an oxygen-glucose deprivation/reperfusion-subjected H9c2 cell line. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide) and lactate dehydrogenases releasing assays showed the effects on cell viability. Immunoblot and flow cytometry assays showed the impact on cell pyroptosis. Enzyme-linked immunosorbent assay uncovered the effects on oxidative stress in H9c2 cells. Further, immunoblot and quantitative polymerase chain reaction assays were conducted to confirm the mechanism. Syringaresinol enhanced the survival and suppressed pyroptosis in H9c2 cells subjected to oxygen-glucose deprivation/reperfusion. Syringaresinol also inhibited oxidative stress in H9c2 cells subjected to oxygen-glucose deprivation/reperfusion, and mechanically, it suppressed the expression of HSP90, thus inhibiting myocardial ischemia/reperfusion injury. Syringaresinol ameliorated the pyroptosis and oxidative stress of oxygen-glucose deprivation/reperfusion in cardiomyocytes and alleviated cardiomyocyte damage.

ROS-Suppression Nanoplatform Combined Activation of STAT3/Bcl-2 Pathway for Preventing Myocardial Infarction in Mice.

Myocardial infarction (MI) is the leading cause of death worldwide. The most effective way to treat myocardial infarction is to rescue ischemic cardiomyocytes. After an ischemic event, the overproduction of reactive oxygen species (ROS) is a key driver of myocardial injury. The produced ROS affects mitochondrial function and induces apoptosis in cardiomyocytes. This was accomplished by constructing platelet-membrane-encapsulated ROS-responsive drug-releasing nanoparticles (PMN@NIC-MalNPs) to deliver malonate and niclosamide (NIC). The results revealed that PMN@NIC-MalNPs degraded and released malonate and niclosamide in a high-level ROS microenvironment, effectively reducing the oxidative stress and apoptosis rate. By enhancing basal mitochondrial oxygen consumption rate (OCR), adenosine triphosphate (ATP) production, and spare respiratory capacity (SRC) in vitro, reduced the oxidative stress levels and restored mitochondrial function. In vivo studies revealed that the PMN@NIC-MalNPs improved cardiac dysfunction, inhibited succinate dehydrogenase (SDH) activity, increased ATP production, and reduced the myocardial infarct size in myocardial infarction model mice. Further, transcriptome analysis and Western blot revealed that PMN@NIC-MalNPs prevented apoptosis by activating the expressions of the signal transducer and activator of transcription 3 (STAT3) and Bcl-2, and inhibiting the expression of Bax. Thus, this study provides a novel therapeutic solution for treating myocardial infarction and predicting the viability of an antioxidant and antiapoptotic therapeutic solution in the treatment of myocardial injury.

Establishment of high-sensitivity cardiac troponin I reference interval for a hospitalized paediatric population under improved selection criteria in the Shandong area

Abstract Objectives This study aimed to evaluate the distribution of plasma troponin I concentration and establish the 99th percentile reference for hs-cTnI in a hospitalized population without a cardiovascular discharge diagnosis from the Shandong area. Methods The hs-cTnI data of anonymous paediatric patients were collected from Qingdao University-Affiliated Yantai Yuhuangding Hospital from 2016 to 2020. Indirect methods were used to calculate the hs-cTnI 99th percentile reference of the whole population and different age groups. Fitting curves and corresponding equations were displayed to determine the relationship between age and hs-cTnI level using the analysis of covariate variance. Results Hs-cTnI plasma levels were highest in the first week of life and declined with age in days. This study found significant differences in the troponin reference intervals for children in different age stratification. The serum hs-cTnI concentration decreased with age in days. In some subgroups, hs-cTnI levels between genders showed a significant difference after the analysis of covariance showed that age was the only predictor of hs-cTnI plasma levels. A non-linear relationship was observed between age and hs-cTnI levels. Thus, curvilinear fitting curve equations for each group were constructed to evaluate the possible relationship between age and hs-cTnI concentration. Conclusions During paediatric period, the highest hs-cTnI concentrations were observed in children aged <1 year, especially those under 7 days. This study presented the 99th percentile cut-offs for different age groups in children aged 0–14 years, which can provide a certain reference value for the clinical diagnosis and treatment of myocardial injury in children.

Effect of methoxymine on prevention and treatment of myocardial injury and cardiac function in elderly patients with hypotension during intraspinal anesthesia.

We aimed to investigate the effects of methoxamine to prevent hypotension in the elderly with intraspinal anesthesia (IA) on myocardial injury and cardiac function. A retrospective study was conducted by enrolling sixty elderly patients who underwent femoral head replacement (FHR) under IA in our hospital from August 2019 to August 2020. The patients were divided into two groups according to the random number table method. In the control group (CG) (30 patients), 5 mg of ephedrine was administered sedately when patients developed hypotension (20% below basal blood pressure). In the research group (RG) (30 cases), 2 μg/(kg·h) of methoxamine hydrochloride was given as a constant-rate pump before anesthesia, and 1 mg of methoxamine hydrochloride was administered intraoperatively if hypotension occurred. The hemodynamic [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)], myocardial injury indexes [cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), fatty acid binding protein (FABP), plasma amino-terminal brain natriuretic peptide precursor (NT-proBNP)], cardiac function indexes [systemic vascular resistance (SVR), stroke volume (SV), net percentage ejection time (ET)] were observed before anesthesia (T1), at the end of surgery (T2), and 6 h after surgery (T3) in both groups. The Bruggemann Comfort Score (BCS) and Visual Analog Scale (VAS) scores at T3, 12 h postoperatively (T4) and 24 h postoperatively (T5) in both groups were observed, and the incidence of adverse reactions to intralesional anesthesia in both groups was counted. SBP, DBP and HR at T2 were lower than those at T1 in both groups, and SBP, DBP and HR at T3 were higher than those at T2, and SBP, DBP and HR at T2 and T3 in the RG were higher than those in the CG (p<0.05). In both groups, cTnⅠ, CK-MB and FABP were higher at T2 and T3 than at T1, higher at T3 than at T2, and NT-proBNP was higher at T2 than at T1 and T3, and lower in the RG than in the CG (p<0.05). In both groups, SVR and SV at time point T2 were lower than at time point T1 and ET was higher than at time point T1, SVR and SV at time point T3 were higher than at time point T2 and ET was lower than at time point T2, SVR and SV in the RG were higher than in the CG and ET was lower than in the CG (p<0.05). VAS scores were higher in both groups at T4 and T5 than at T3, and lower in the RG than in the CG (p<0.05). Methoxamine can effectively reduce the risk of hypotension in geriatric endotracheal anesthesia, which can reduce myocardial injury and stabilize cardiac function in patients.

Mechanisms and therapeutic strategies of extracellular vesicles in cardiovascular diseases.

Cardiovascular disease (CVD) significantly impacts global society since it is the leading cause of death and disability worldwide, and extracellular vesicle (EV)-based therapies have been extensively investigated. EV delivery is involved in mediating the progression of CVDs and has great potential to be biomarker and therapeutic molecular carrier. Besides, EVs from stem cells and cardiac cells can effectively protect the heart from various pathologic conditions, and then serve as an alternative treatment for CVDs. Moreover, the research of using EVs as delivery carriers of therapeutic molecules, membrane engineering modification of EVs, or combining EVs with biomaterials further improves the application potential of EVs in clinical treatment. However, currently there are only a few articles summarizing the application of EVs in CVDs. This review provides an overview of the role of EVs in the pathogenesis and diagnosis of CVDs. It also focuses on how EVs promote the repair of myocardial injury and therapeutic methods of CVDs. In conclusion, it is of great significance to review the research on the application of EVs in the treatment of CVDs, which lays a foundation for further exploration of the role of EVs, and clarifies the prospect of EVs in the treatment of myocardial injury.

Integrating serum pharmacochemistry and network pharmacology to explore the molecular mechanisms of Acanthopanax senticosus (Rupr. & Maxim.) Harms on attenuating doxorubicin-induced myocardial injury

Ethnopharmacological relevanceAcanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. or Siberian ginseng, has a rich history of use as an adaptogen, a substance believed to increase the body's resistance to stress, fatigue, and infectious diseases. As a traditional Chinese medicine, AS is popular for its cardioprotective effects which can protect the cardiovascular system from hazardous conditions. Doxorubicin (DOX), on the other hand, is a first-line chemotherapeutic agent against a variety of cancers, including breast cancer, lung cancer, gastric cancer, and leukemia, etc. Despite its effectiveness, the clinical use of DOX is limited by its side effects, the most serious of which is cardiotoxicity. Considering AS could be applied as an adjuvant to anticancer agents, the combination of AS and DOX might exert synergistic effects on certain malignancies with mitigated cardiotoxicity. Given this, it is necessary and meaningful to confirm whether AS would neutralize the DOX-induced cardiotoxicity and its underlying molecular mechanisms. Aim of the studyThis paper aims to validate the cardioprotective effects of AS against DOX-induced myocardial injury (MI) while deciphering the molecular mechanisms underlying such effects. Materials and methodsFirstly, the cardioprotective effects of AS against DOX-induced MI were confirmed both in vitro and in vivo. Secondly, serum pharmacochemistry and network pharmacology were orchestrated to explore the in vivo active compounds of AS and predict their ways of functioning in the treatment of DOX-induced MI. Finally, the predicted mechanisms were validated by Western blot analysis during in vivo experiments. ResultsThe results demonstrated that AS possessed excellent antioxidative ability, and could alleviate the apoptosis of H9C2 cells and the damage to mitochondria induced by DOX. In vivo experiments indicated that AS could restore the conduction abnormalities and ameliorate histopathological changes according to the electrocardiogram and cardiac morphology. Meanwhile, it markedly downregulated the inflammatory factors (TNF-α, IL-6, and IL-1β), decreased plasma ALT, AST, LDH, CK, CK-MB, and MDA levels, as well as increased SOD and GSH levels compared to the model group, which collectively substantiate the effectiveness of AS. Afterward, 14 compounds were identified from different batches of AS-dosed serum and selected for mechanism prediction through HPLC-HRMS analysis and network pharmacology. Consequently, the MAPKs and caspase cascade were confirmed as primary targets among which the interplay between the JNK/Caspase 3 feedback loop and the phosphorylation of ERK1/2 were highlighted. ConclusionsIn conclusion, the integrated approach employed in this paper illuminated the molecular mechanism of AS against DOX-induced MI, whilst providing a valuable strategy to elucidate the therapeutic effects of complicated TCM systems more reliably and efficiently.

Possible Mechanisms of SARS-CoV2-Mediated Myocardial Injury

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly become a global health emergency. In addition to causing respiratory effects, SARS-CoV-2 can result in cardiac involvement leading to myocardial damage, which is increasingly being explored in the literature. Myocardial injury is an important pathogenic feature of COVID-19. The angiotensin-converting enzyme-2 receptor plays a key role in the pathogenesis of the virus, serving as a “bridge” allowing SARS-CoV-2 to invade the body. However, the exact mechanism underlying how SARS-CoV-2 causes myocardial injury remains unclear. This review summarizes the main possible mechanisms of myocardial injury in patients with COVID-19, including direct myocardial cell injury, microvascular dysfunction, cytokine responses and systemic inflammation, hypoxemia, stress responses, and drug-induced myocardial injury. Understanding of the underlying mechanisms would aid in proper identification and treatment of myocardial injury in patients with COVID-19.

Long non-coding RNA Sox2OT promotes coronary microembolization-induced myocardial injury by mediating pyroptosis.

ObjectiveAs a common complication of coronary microembolization (CME), myocardial injury (MI) implies high mortality. Long non‐coding RNAs (lncRNAs) are rarely studied in CME‐induced MI. Herein, this study intended to evaluate the role of lncRNA Sox2 overlapping transcript (Sox2OT) in CME‐induced MI.MethodsThe CME rat models were successfully established by injection of microemboli. Rat cardiac functions and MI were observed by ultrasonic electrocardiogram, HE staining, and HBFP staining. Functional assays were utilized to test the inflammatory responses, oxidative stress, and pyroptosis using reverse transcription quantitative polymerase chain reaction, Western blotting, immunohistochemistry, immunofluorescence, and ELISA. Dual‐luciferase reporter gene assay and RNA immunoprecipitation were conducted to clarify the targeting relations between Sox2OT and microRNA (miRNA)‐23b and between miR‐23b and toll‐like receptor 4 (TLR4).ResultsRat CME disrupted the cardiac functions and induced inflammatory responses and oxidative stress, and activated the nuclear factor‐kappa B (NF‐κB) pathway and pyroptosis (all P < 0.05). An NF‐κB inhibitor downregulated the NF‐κB pathway, reduced pyroptosis, and relieved cardiomyocyte injury and pyroptosis. Compared with the sham group (1.05 ± 0.32), lncRNA Sox2OT level (4.41 ± 0.67) in the CME group was elevated (P < 0.05). Sox2OT acted as a competitive endogenous RNA (ceRNA) of miR‐23b to regulate TLR4. Silencing of Sox2OT favoured miR‐23b binding to 3′UTR of TLR4 mRNA leading to suppressed TLR4‐mediated NFKB signalling and pyroptosis in myocardial tissues harvested from CME rat models. In addition, miR‐23b overexpression could supplement the cytosolic miR‐23b reserves to target TLR‐4 and partially reverse Sox2OT‐mediated pyroptosis in LPS‐treated H9C2 cells.ConclusionsThis study supported that silencing Sox2OT inhibited CME‐induced MI by eliminating Sox2OT/miR‐23b binding and down‐regulating the TLR4/NF‐κB pathway. This investigation may provide novel insights for the treatment of CME‐induced MI.

Effects and Mechanisms of Taohong Siwu Decoction on the Prevention and Treatment of Myocardial Injury.

Taohong Siwu decoction (THSWD) is one of the classic prescriptions for promoting blood circulation and removing blood stasis. With the continuous in-depth excavation in basic and clinical research, it has been found that THSWD has made greater progress in the prevention and treatment of cardiovascular diseases. Mechanisms of the current studies have shown that it could prevent and treat the myocardial injury by inhibiting inflammatory reaction, antioxidant stress, inhibiting platelet aggregation, prolonging clotting time, anti-fibrosis, reducing blood lipids, anti-atherosclerosis, improving hemorheology and vascular pathological changes, regulating related signal pathways and other mechanisms to prevent and treat the myocardial injury, so as to protect cardiomyocytes and improve cardiac function. Many clinical studies have shown that THSWD is effective in the prevention and treatment of cardiovascular diseases related to myocardial injuries, such as coronary heart disease angina pectoris (CHD-AP), and myocardial infarction. In clinical practice, it is often used by adding and subtracting prescriptions, the combination of compound prescriptions and combinations of chemicals and so on. However, there are some limitations and uncertainties in both basic and clinical research of prescriptions. According to the current research, although the molecular biological mechanism of various active ingredients needs to be further clarified, and the composition and dose of the drug have not been standardized and quantified, this study still has exploration for scientific research and clinical practice. Therefore, this review mainly discusses the basic mechanisms and clinical applications of THSWD in the prevention and treatment of the myocardial injury caused by CHD-AP and myocardial infarction. The authors hope to provide valuable ideas and references for researchers and clinicians.

Therapeutic Potential of Exosomes Derived From circRNA_0002113 Lacking Mesenchymal Stem Cells in Myocardial Infarction.

Exosomes are participated in the pathogenesis of cardiovascular diseases and can be secreted by mesenchymal stem cells (MSCs). However, the effects of circRNA, delivered by exosomes derived from MSCs, on myocardial injury remain unclear. Hence, this study aims to explore the therapeutic potential of exosomes derived from circRNA_0002113 lacking MSCs in the treatment of myocardial injury in vitro and in vivo. Our results reveal that exosomes derived from circRNA_0002113 lacking MSCs decreased cell apoptosis in anoxia-reoxygenation (A/R) model cells, and reduced myocardial injury by inhibiting nuclear translocation of RUNX1 in vitro and in vivo. Moreover, miR-188-3p, which targets RUNX1 in cardiomyocytes was also found to interact with circRNA_0002113. In conclusion, exosomes derived from circRNA_0002113 lacking MSCs could suppress myocardial infarction by sponging miR-188-3p to regulate RUNX1 nuclear translocation. The circRNA_0002113/miR-188-3p/RUNX1 axis mediated alleviation of apoptosis serves as a novel strategy to treat myocardial I/R injury.

Kuanxiong aerosol inhibits apoptosis and attenuates isoproterenol-induced myocardial injury through the mitogen-activated protein kinase pathway

Ethnopharmacological relevanceKuanxiong aerosol (KXA) is a common clinical drug based on Fangxiang Wentong (FXWT) therapy in the treatment of angina pectoris. However, the pharmacological mechanism of KXA in the prevention and treatment of myocardial injury (MI) is not clear. Aim of the studyThe purpose of this study was to explore the protective effect of KXA on isoproterenol (ISO)-induced MI in rats. Materials and methodsThe study included male Wistar Kyoto rats (age: 6 weeks). The rats were randomly divided into the following 5 groups (n = 6 per group): control group, ISO group, isosorbide mononitrate (ISMN) group (5 mg/kg), KXA-L group (0.1 mL/kg), and KXA-H group (0.3 mL/kg). The rats in the last three groups were given intragastric administration for 14 days, and rats in control group and ISO group were given the same amount of normal saline daily. ISO (120 mg/kg) was used to induce MI on the 13th and 14th days. We assessed electrocardiograms (ECGs), myocardial specific enzymes, histopathological changes, and apoptosis. ResultsWe found that KXA reduced the increase in the ST-segment amplitude (elevation or depression) and the levels of myocardial marker enzymes induced by ISO in MI rats, improved the pathological changes in myocardial tissue, and reduced cardiomyocyte apoptosis. At the same time, KXA significantly inhibited the up-regulation of caspase-3 and Bax expression and down-regulation of Bcl-2 expression induced by ISO. RNA sequencing showed that 90 up-regulated genes induced by ISO were down-regulated after KXA treatment, whereas 27 down-regulated genes induced by ISO were up-regulated after KXA treatment. In addition, KEGG pathway enrichment analysis showed that the mitogen-activated protein kinase (MAPK) signaling pathway may be an important target of KXA in the treatment of ISO-induced MI in rats. The results of RNA sequencing verified by Western blot analysis showed that KXA significantly inhibited the activation of the ISO-induced MAPK pathway. ConclusionsKXA improves cardiac function in MI rats by inhibiting apoptosis mediated by the MAPK signaling pathway.

Expert consensus statement on the diagnosis and treatment of fulminant myocarditis in the context of the COVID-19 pandemic

The article contains Russian expert consensus statement on the diagnosis and treatment of fulminant myocarditis (FM), prepared by the National Society for the Study of Lipidology and Associated Metabolic Diseases, the Society of Internal, Sports and Preventive Medicine based on the clinical guidelines of the Russian Society of Cardiology, results of China Clinical Study (NCT03268642), Expert Guidelines of Russian Clinical and Research Center of Gerontology, Chinese Society of Geriatrics, Cardiology Branch of Beijing Medical Association. Pathogenesis, diagnosis and treatment of myocardial injury and FM in patients infected with SARS-CoV-2 in the context of the COVID-19 pandemic are discussed. Clinical features and diagnostic criteria of FM, as well as and comprehensive therapy for myocardial injury and FM are presented. The proposed protocol for the management of patients with myocardial injury in patients infected with SARS-CoV-2 was adapted with the clinical experience of Chinese experts. The protocol for anticoagulant and antiplatelet therapy was proposed by the Moscow State University Medical Center.

Abstract 15010: Myocardial Injury in Sepsis With Acute Respiratory Distress Syndrome

Introduction: Sepsis is common and associated with high morbidity and mortality; novel prognostic biomarkers are needed. The association of myocardial injury with mortality in sepsis has not been fully characterized. Hypothesis: We hypothesized that elevated plasma high-sensitivity troponin I (hs-TnI) would be associated with 60-day mortality in patients with sepsis and acute respiratory distress syndrome (ARDS). Methods: We conducted a retrospective multicenter cohort study of subjects from the MI-ARDS study with ARDS and sepsis. The exposure variable was plasma hs-TnI on intubation (Day 0) and Day 3. Hs-TnI was measured using Abbott Laboratories’ ARCHITECT STAT assay. Patients were divided into four hs-TnI (ng/L) groups (Grp): GrpA: &lt;2 (undetectable), GrpB: ≥2-&lt;26 (&lt;99 th percentile of population), GrpC: ≥26-&lt;130 (&lt;5 times upper limit of normal [ULN]), GrpD: ≥130 (&gt;5 times ULN). The primary outcome was 60-day mortality. We determined the association between hs-TnI and mortality using Cox proportional hazards models. Results: Of 320 subjects, there were 15 (4%) in GrpA, 97 (30%) in GrpB, 88 (28%) in GrpC, and 120 (38%) in GrpD. Mean age was 50 years and 172 subjects (54%) required vasopressors. Higher plasma levels of hs-TnI were associated with higher SOFA score and creatinine, and more vasopressor use. Overall mortality was 33%. There was no significant difference in 60-day survival between clinical categories of Day 0 hs-TnI (Fig 1-A). Rising troponin between Day 0 and Day 3 was associated with a higher risk of mortality after adjusting for age, sex, trial assignment, and SOFA score (HR: 1.75, CI: 1.11-2.77, p=0.02) (Fig 1-B), and additionally adjusting for Day 0 hs-TnI (HR: 1.72, CI: 1.03-2.85, p=0.04). Conclusions: Initial hs-TnI in patients with sepsis and ARDS was not associated with mortality. Increase in hs-TnI of at least 20% by Day 3 was associated with 60-day mortality. Future studies should assess mechanism and treatment of myocardial injury in sepsis.

Guanxinshutong capsule ameliorates cardiac function and architecture following myocardial injury by modulating ventricular remodeling in rats

Guanxinshutong capsule (GXST), which consists of five traditional Chinese medicines, has been used for a long time in China for the treatment of cardiovascular diseases, such as coronary artery disease and myocardial infarction. However, the effects on GXST on myocardial injury (MI) have not been studied in detail. In these experiments, we found that GXST administration decreased MI-associated ventricular remodeling (VR) with a reduction in interventricular septal thickness in diastole (IVSd), left ventricular posterior wall diameter in systole (LVPWs), and left ventricular posterior wall diameter in diastole (LVPWd) to ameliorate cardiac function and architecture, as measured by echocardiography. Furthermore, histological analysis showed that GXST could ameliorate pathological alterations in the myocardium. And Sirius red staining, wheat germ agglutinin staining and inflammation-related immunohistochemistry results showed that GXST ameliorated the fibrosis areas, cardiac hypertrophy and inflammation (IL-6 and TNF-α). In addition, GXST upregulated intercellular junction proteins (N-cad and Cx-43) and downregulated the angiogenesis-related proteins (PDGF and VEGFA), myocardial fibrosis-related proteins (TGF-β1), and matrix metalloproteinase (MMP-2 and MMP-9). We also found that GXST medium-dose group (1 g/kg/d) dosage was the most efficacious. In conclusion, GXST protected cardiac tissues against MI by reducing VR, thus indicating the potential application of GXST in the treatment of MI.

Progress in Treatment of Myocardial Injury in Patients with 2019-nCoV: A Chinese Experience.

Since December 2019, the 2019 novel coronavirus (2019-nCoV) infection began to appear in Hubei Province of China and gradually spread to other provinces and other countries. The virus has the characteristics of strong transmission capacity, diverse clinical manifestations, long incubation period, and latent infection, thus posing a serious threat to human life safety and health. With the increasing number of cases and the continuous enrichment of clinical data, 2019-nCoV-infected patients have received more and more attention regarding myocardial injury related to virus infection besides typical respiratory system manifestations. According to the published data, we summarize the myocardial injury manifestations, characteristics, effects on disease condition, and prognosis of 2019-nCoV-infected patients and discuss the possible injury mechanism, treatment methods, and future research directions.

Prevention and Treatment of Cancer Therapeutics-related Cardiac Dysfunction

Cancer therapeutics-related cardiac dysfunction(CTRCD)is receiving more attention.Risk factors assessment before cancer therapy,cardiac function monitoring during and after cancer therapy,and early detection and treatment of myocardial injury are key to preventing clinical heart failure.The incidence and severity of cardiotoxicity can be reduced by measures such as reducing drug dose,adjusting administration route,and using low toxic drugs.Cardioprotective agents including anti-heart failure drugs and dexrazoxane are important for the prevention and treatment of CTRCD.Patients with advanced heart failure may also benefit from mechanical treatments including cardiac resynchronization therapy and mechanically-assisted ventricular devices.This article reviews the recent advances in the prevention and treatment of CTRCD.

Myocardial regeneration: role of epicardium and implicated genes.

Lower invertebrates' hearts such as those of zebrafish have the capacity for scarless myocardial regeneration which is lost by mammalian hearts as they form a fibrotic scar tissue instead of regenerating the injured area. However, neonatal mammalian hearts have a remarkable capacity for regeneration highlighting conserved evolutionary mechanisms underlying such a process. Studies investigated the underlying mechanism of myocardial regeneration in species capable to do so, to see its applicability on mammals. The epicardium, the mesothelial outer layer of the vertebrate heart, has proven to play an important role in the process of repair and regeneration. It serves as an important source of smooth muscle cells, cardiac fibroblasts, endothelial cells, stem cells, and signaling molecules that are involved in this process. Here we review the role of the epicardium in myocardial regeneration focusing on the different involved; Activation, epithelial to mesenchymal transition, and differentiation. In addition, we will discuss its contributory role to different aspects that support myocardial regeneration. Of these we will discuss angiogenesis and the formation of a regenerate extracellular matrix. Moreover, we will discuss several factors that act on the epicardium to affect regeneration. Finally, we will highlight the utility of the epicardium as a mode of cell therapy in the treatment of myocardial injury.

Macrophage Polarization as a Therapeutic Target in Myocardial Infarction.

Myocardial infarction is characterized by the interruption of blood flow through the heart, directly causing mortality and disability worldwide. Cardiac macrophages exhibit distinct phenotypes (e.g., M1 or M2) and functions (e.g., proinflammatory or anti-inflammatory) in response to the alterations of myocardial microenvironment, and subsequently exacerbate or resolve inflammation in the infarcted hearts. Regulation of macrophage polarization was implicated in myocardial infarction for the quality and outcome of cardiac healing. The purpose of this review was to summarise the current understanding on the regulation of macrophage polarization in myocardial infarction and highlight the therapeutic potential of pharmacological regulators in the treatment of myocardial injury via modulating macrophage polarization. Timely control of M2/M1 ratio by endogenous mediators and pharmacological regulators should help the resolution of inflammation, promote wound healing and prevent cardiac fibrosis after myocardial infarction. Macrophage polarization deserves better investigations as the therapeutic target for the development of novel drugs against myocardial injury.

Establishment of myocardial targeted nanoparticles and preliminary evaluation of its effects on prevention and treatment of myocardial injury

Establishment of myocardial targeted nanoparticles and preliminary evaluation of its effects on prevention and treatment of myocardial injury

Role of levothyroxine and vitamin E supplementation in the treatment of oxidative stress-induced injury and apoptosis of myocardial cells in hypothyroid rats.

To explore the underlying mechanism and treatment of myocardial injury caused by hypothyroidism, we evaluated oxidative stress in serum and myocardial tissue of hypothyroid rats. The effect of levothyroxine (LT4) replacement therapy and vitamin E (VitE) supplementation on oxidative stress-induced injury and apoptosis of myocardial tissue is examined. Male Sprague-Dawley rats were divided into five groups: normal control group, propylthiouracil group (PTU group), LT4 treatment group (PTU + LT4 group), vitamin E treatment group (PTU + VitE group), and combined treatment group (PTU + LT4 + VitE group). Superoxide dismutase (SOD) activity and malondialdehyde (MDA) expression in serum and myocardium were determined. Myocardial apoptosis index (AI) in each group was determined by TUNEL assay. SOD levels in serum were significantly increased in PTU + VitE and PTU + LT4 + Vit E groups, as compared to that in PTU and PTU + LT4 groups (P < 0.05). MDA levels in serum and myocardial tissue were significantly lower in PTU + LT4, PTU + VitE, and PTU + LT4 + VitE groups, as compared to that in the PTU group (P < 0.05). Myocardial apoptosis was significantly increased in PTU and PTU + VitE groups as compared to that in the normal control group (P < 0.05), while it was significantly lower in PTU + LT4 and PTU + LT4 + VitE groups, as compared to that in the PTU group (P < 0.05). In this study, levothyroxine replacement therapy and vitamin E supplementation appeared to ameliorate myocardial apoptosis in hypothyroid rats, the mechanism of which appears to be related to improved thyroid function and reduced oxidative stress.