Myocardial Inflammatory Response Research Articles

Black phosphorus quantum dots induce myocardial inflammatory responses and metabolic disorders in mice

As an ultrasmall derivative of black phosphorus (BP) sheets, BP quantum dots (BP-QDs) have been effectively used in many fields. Currently, information on the cardiotoxicity induced by BP-QDs remains limited. We aimed to evaluate BP-QD-induced cardiac toxicity in mice. Histopathological examination of heart tissue sections was performed. Transcriptome sequencing, real-time quantitative PCR (RT‒qPCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) assays were used to detect the mRNA and/or protein expression of proinflammatory cytokines, nuclear factor kappa B (NF-κB), phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT), peroxisome proliferator-activated receptor gamma (PPARγ), and glucose/lipid metabolism pathway-related genes. We found that heart weight and heart/body weight index (HBI) were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 days. In addition, obvious inflammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated groups. Altered expression of proinflammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced inflammatory responses. In addition, BP-QD treatment also affected the PI3K-AKT, PPARγ, thermogenesis, oxidative phosphorylation, and cardiac muscle contraction signaling pathways. The expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure, and the effect was primarily mediated by the PPAR signaling pathway. Our study provides new insights into the toxicity of BP-QDs to human health.

Neprilysin Inhibition in the Prevention of Anthracycline-Induced Cardiotoxicity.

Anthracycline-induced cardiotoxicity (AIC) poses a clinical challenge in the management of cancer patients. AIC is characterized by myocardial systolic dysfunction and remodeling, caused by cardiomyocyte DNA damage, oxidative stress, mitochondrial dysfunction, or renin-angiotensin-aldosterone system (RAAS) dysregulation. In the past decade, after positive results of a PARADIGM-HF trial, a new class of drugs, namely angiotensin receptor/neprilysin inhibitors (ARNi), was incorporated into the management of patients with heart failure with reduced ejection fraction. As demonstrated in a variety of preclinical studies of cardiovascular diseases, the cardioprotective effects of ARNi administration are associated with decreased oxidative stress levels, the inhibition of myocardial inflammatory response, protection against mitochondrial damage and endothelial dysfunction, and improvement in the RAAS imbalance. However, data on ARNi's effectiveness in the prevention of AIC remains limited. Several reports of ARNi administration in animal models of AIC have shown promising results, as ARNi prevented ventricular systolic dysfunction and electrocardiographic changes and ameliorated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and the inflammatory response associated with anthracyclines. There is currently an ongoing PRADAII trial aimed to assess the efficacy of ARNi in patients receiving breast cancer treatment, which is expected to be completed by late 2025.

Analysis of the Relationship between Circulating NT-proBNP and Myocardial Injury, Inflammatory Response and Coronary Collateral Circulation in Acute Myocardial Infarction before Clopidogrel Treatment

Analysis of the Relationship between Circulating NT-proBNP and Myocardial Injury, Inflammatory Response and Coronary Collateral Circulation in Acute Myocardial Infarction before Clopidogrel Treatment

Knockdown of histone deacetylase 9 attenuates sepsis-induced myocardial injury and inflammatory response.

Myocardial cell damage is associated with apoptosis and excessive inflammatory response in sepsis. Histone deacetylases (HDACs) are implicated in the progression of heart diseases. This study aims to explore the role of histone deacetylase 9 (HDAC9) in sepsis-induced myocardial injury. Lipopolysaccharide (LPS)-induced Sprague Dawley rats and cardiomyocyte line H9C2 were used as models in vivo and in vitro. The results showed that HDAC9 was significantly upregulated after LPS stimulation, and HDAC9 knockdown remarkably improved cardiac function, as evidenced by decreased left ventricular internal diameter end diastole (LVEDD) and left ventricular internal diameter end systole (LVESD), and increased fractional shortening (FS)% and ejection fraction (EF)%. In addition, HDAC9 silencing alleviated release of inflammatory cytokines (tumor necrosis factor-α (TNF-α), IL-6 and IL-1β) and cardiomyocyte apoptosis in vivo and in vitro. Furthermore, HDAC9 inhibition was proved to suppress nuclear factor-kappa B (NF-κB) activation with reducing the levels of p-IκBα and p-p65, and p65 nuclear translocation. Additionally, interaction between miR-214-3p and HDAC9 was determined through bioinformatics analysis, RT-qPCR, western blot and dual luciferase reporter assay. Our data revealed that miR-214-3p directly targeted the 3'UTR of HDAC9. Our findings demonstrate that HDAC9 suppression ameliorates LPS-induced cardiac dysfunction by inhibiting the NF-κB signaling pathway and presents a promising therapeutic agent for the treatment of LPS-stimulated myocardial injury.

Study on Maslinic Acid Inhibiting Cardiomyocyte Pyrolysis by Regulating TLR4/NFκB/NLRP3 Signaling Pathway

Background: The paper aimed to investigate the effects of Maslinic acid on myocardial injury caused by ischemia and hypoxia after acute myocardial infarction, and to explore the mechanism of Maslinic acid inhibiting local inflammation and myocardial cell pyrolysis, slowing down the synthesis of extracellular matrix, improving myocardial fibrosis and remodeling ventricle. Materials and Methods: Wistar rats with acute myocardial infarction were used. The serum levels of TNF-α, IL-1β, CRP, and LDH were detected by ELISA. The expressions of inflammation-related proteins such as TLR4, NFκB, NLRP3, IL-10, and TGF-β in myocardial infarction were detected by Western-blot. TUNEL method was employed to detect myocardial cell pyrolysis. Masson staining was used to detect myocardial fibrosis. Immunohistochemical method was applied to detect the expressions of CD206 and CD11C to understand the polarization of macrophages. Results: Maslinic acid can inhibit the levels of inflammatory factors such as CRP, TNF-α and IL-1β, and reduce the expression of myocardial TLR4, NFκB, NLRP3 and other inflammation-related proteins after myocardial infarction. The release of LDH is significantly reduced. The expression of TUNEL positive cells in myocardium is obviously reduced after myocardial infarction. Maslinic acid can increase the expression of CD206-positive cells and reduce the expression of CD11C-positive cells, thus regulate and promote polarization into M2 macrophages. Conclusion: Maslinic acid may inhibit myocardial cell pyrolysis and inflammatory response by regulating the TLR4/NFκB/NLRP3 signaling pathway. Maslinic acid can improve myocardial fibrosis by inhibiting myocardial cell pyrolysis and regulating the polarization of macrophages.

Hypoxia Induces M2 Macrophages to Express VSIG4 and Mediate Cardiac Fibrosis After Myocardial Infarction.

M2 macrophage-mediated tissue repair plays an important role in acute myocardial infarction (AMI). Additionally, VSIG4, which is mainly expressed on tissue-resident and M2 macrophages, is crucial for the regulation of immune homeostasis; however, its effects on AMI remain unknown. In this study, we aimed to investigate the functional significance of VSIG4 in AMI using VSIG4 knockout and adoptive bone marrow transfer chimeric models. We also determined the function of cardiac fibroblasts (CFs) through gain- or loss-of-function experiments. We showed that VSIG4 promotes scar formation and orchestrates the myocardial inflammatory response after AMI, while also promoting TGF-β1 and IL-10. Moreover, we revealed that hypoxia promotes VSIG4 expression in cultured bone marrow M2 macrophages, ultimately leading to the conversion of CFs to myofibroblasts. Our results reveal a crucial role for VSIG4 in the process of AMI in mice and provide a potential immunomodulatory therapeutic avenue for fibrosis repair after AMI.

Gender Differences in the Correlations Between Immune Cells and Organ Damage Indexes of Acute Myocardial Infarction Patients.

There are clear gender differences in the pathological process and outcome in acute myocardial infarction (AMI) patients but inflammatory responses remain clarified. Here, we aimed to analyse the correlations between inflammatory cells and organ injury parameters in AMI patients and compared between male and female groups. A total of 603 AMI patients who underwent percutaneous coronary intervention (PCI) within 24 hours of the onset were analysed retrospectively. Basic information and hematological parameters detected 6 hours before the PCI were collected, neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) were calculated. Renal, liver function indicators, and myocardial enzymes were measured. Left ventricular ejection fraction (EF) and fractional shortening (FS) on days 5-7 after PCI were obtained. Western blot was performed to detect iNOS, eNOS and nNOS expression in H9C2 rat cardiomyocytes treated with IL-6 with and without estrogen and testosterone. WBC, NEU, MON, MLR, CK, ALT and CREA of male patients were significantly higher than females, but FS was lower in females. NEU, MON and MLR were positively correlated with CK, CK-MB, AST, and ALT in males, whereas LYM were correlated with these parameters in female. NEU and NLR were inversely correlated with EF or FS only in female. Estrogen and testosterone reduced IL-6-induced iNOS protein expression in H9C2 cardiomyocytes, estrogen enhanced IL-6-induced nNOS protein expression. NEU, MON, MLR in male AMI patients, and LYM in female patients were associated with organ injury parameters. Estrogen regulation of nitric oxide pathway may mediate the protective effects in female.

Silencing of Long Noncoding RNA TUG1 Ameliorates Atherosclerosis-Induced Myocardial Injury by Upregulating microRNA-30b-3p and Downregulating Brd4.

Long noncoding RNAs and microRNAs (miRNAs) are emerging biomarkers involved in human diseases, and we focused on the roles of long noncoding RNA taurine upregulated gene 1 (TUG1) and miR-30b-3p in the related mechanisms of atherosclerosis-induced myocardial injury. ApoE-deficient mice were fed with high-fat diet to establish atherosclerotic models and then were subjected to either TUG1 downregulation or miR-30b-3p upregulation treatment. The serum myocardial enzymes, inflammatory biomarkers, pathological changes, intramyocardial macrophage infiltration, and apoptosis of cardiomyocytes in atherosclerotic mice were determined. The expression of TUG1, miR-30b-3p, and bromodomain protein 4 (Brd4) in atherosclerotic models was evaluated. Moreover, the correlations of TUG1, miR-30b-3p, and Brd4 were verified. TUG1 and Brd4 were increased while miR-30b-3p was decreased in atherosclerotic mice. The silenced TUG1 or elevated miR-30b-3p attenuated atherosclerosis-induced myocardial injury mainly by reducing serum myocardial enzyme content and inflammatory response, improving pathological changes, and preventing macrophage infiltration and cardiomyocyte apoptosis in atherosclerotic mice. Mechanistically, TUG1 could competitively bind with miR-30b-3p to prevent the degradation of its target gene Brd4. This study reveals that the silencing of TUG1 ameliorates atherosclerosis-induced myocardial injury by upregulating miR-30b-3p and downregulating Brd4, which may provide novel targets for atherosclerosis treatment.

QishenYiqi dripping pill protects against myocardial ischemia/reperfusion injury via suppressing excessive autophagy and NLRP3 inflammasome based on network pharmacology and experimental pharmacology.

Background: Myocardial ischemia/reperfusion (I/R) injury is associated with multiple serious clinical manifestations. Autophagy is upregulated in a short period of ischemia and further enhanced during reperfusion phase, which was considered as a “double-edged sword” in the pathological process of myocardial I/R injury. In addition, NLRP3 inflammasome triggers myocardial inflammatory response, which leads to cardiomyocyte death via pyroptosis and promotes subsequent myocardial remodelling. Qishen Yiqi Dripping Pill (QSYQ) has been recognized as a potential protective agent of cardiovascular diseases. Objective: We predicted the bioactive compounds, targets and pathways of OSYQ intervening on myocardial I/R injury by network pharmacology. Furthermore, we investigated the effect of QSYQ on myocardial I/R injury and explored its underlying mechanism via autophagy and NLRP3 Inflammasome. Methods: Bioactive compounds, targets of QSYQ and relevant targets of myocardial I/R injury were collected from public databases. The protein-protein interaction network, Gene ontology and KEGG pathway enrichment analysis were carried out to screen the key compounds, target genes, functional annotation and pivotal pathways. Molecular docking was used to validate the binding association between target genes and key bioactive ingredients. Furthermore, sixty SD rats were randomized into four groups: 1) sham, 2) model, 3) captopril and 4) QSYQ pretreatment (14 days before and after surgery). Each arm was subjected to ischemia/reperfusion surgery except sham arm (30 min coronary ligation, then reperfusion). Left ventricular (LV) function were evaluated and the hearts were used to evaluate size of myocardial infarction, cardiomyocyte fibrosis, and myocardial autophagosomes. Results: The network pharmacology revealed the mechanism of QSYQ intervening on myocardial I/R injury might be related to NOD-like receptor signaling pathway, PI3K-Akt signaling pathway, autophagy-animal, etc., Molecular-docking suggested the core target proteins had good binding association with bioactive compounds of QSYQ. The experiment confirmed that QSYQ attenuated myocardial infarct size, decreased inflammatory infiltration and collagen fiber deposition and alleviated the autophagosome and myocardium ultrastructure injury, leading to LV systolic function improvement. The possible mechanism of cardioprotection was due to regulating autophagy-related proteins, activating PI3K/Akt-mTOR signaling pathway, and inhibiting activation and assembly of NLRP3 inflammasome. Conclusion: QSYQ ameliorated myocardial I/R injury via suppressing excessive autophagy and NLRP3 Inflammasome.

Effect of Qishen granules on isoproterenol-induced chronic heart failure in rats evaluated by comprehensive metabolomics.

Qishen granules (QSG), a Chinese herbal formula, has been widely used in the treatment of myocardial ischemic chronic heart failure (CHF) for many years, but its mechanism of action is still unclear. In this study, comprehensive metabolomics was used to investigate the underlying protective mechanisms of QSG in an isoproterenol-induced CHF rat model. A total of 14 biomarkers were identified in serum and 34 biomarkers in urine, which were mainly related to fatty acid metabolism, bile acid metabolism, amino acid metabolism, purine metabolism, vitamin metabolism, and inflammation. Finally, 22 markers were selected for quantitative analysis of serum, urine, and fecal samples to verify the reliability of the results of untargeted metabolomics, and the results were similar to those of untargeted metabolomics. The correlation analysis showed that the targeted quantitative endogenous metabolites and CHF-related indexes were closely related. QSG might alleviate myocardial inflammatory response, oxidative stress, and amino acid metabolism disorder in CHF by regulating the level of endogenous metabolites. This study revealed QSG could regulate potential biomarkers and correlated metabolic pathway, which provided support for the further application of QSG.

Naltrexone-Induced Cardiac Function Improvement is Associated With an Attenuated Inflammatory Response and Lipid Perioxidation in Volume Overloaded Rats.

In previous studies, upregulation of myocardial opioid receptors as well as the precursors of their endogenous ligands were detected in the failing heart due to chronic volume overload. Moreover, opioid receptor blockade by naltrexone improved left ventricular function. In parallel, inflammatory processes through cytokines have been confirmed to play an important role in the pathogenesis of different forms of heart failure. Thus, the present study examined the systemic and myocardial inflammatory response to chronic volume overload and its modulation by chronic naltrexone therapy. Chronic volume overload was induced in male Wistar rats by applying an infrarenal aortocaval fistula (ACF) for 28 days during which the selective opioid receptor antagonist naltrexone (n = 6) or vehicle (n = 6) were administered via a subcutaneously implanted Alzet minipump. The ultrastructural, morphometric and hemodynamic characterization of ACF animals were performed using an intraventricular conductance catheter in vivo and electron microscopy in vitro. Co-localization of mu-, delta- and kappa-opioid receptor subtypes (MOR, DOR, and KOR respectively) with the voltage gated L-type Ca2+ channel (Cav1.2), the ryanodine receptor (RyR), and mitochondria in cardiomyocytes as well as IL-6, IL-12, TNF-alpha, and Malondialdehyde (MDA) were determined using double immunofluorescence confocal microscopy, RT-PCR and ELISA, respectively. In rat left ventricular myocardium, three opioid receptor subtypes MOR, DOR, and KOR colocalized with Cav1.2, RyR and mitochondria suggesting a modulatory role of the excitation-contraction coupling. In rats with ACF-induced volume overload, signs of heart failure and myocardial ultrastructural damage, chronic naltrexone therapy improved cardiac function and reversed the systemic and myocardial inflammatory cytokine expression as well as lipid peroxidation. In conclusion, antagonism of the cardiodepressive effects of the myocardial opioid system does not only improve left ventricular function but also blunts the inflammatory response and lipid peroxidation.

Curcumin attenuates myocardial ischemia and reperfusion-induced proinflammatory response through activation of the Nrf-2/HO-1 signaling pathway

Acute myocardial infarction (MI) is a global issue with high incidence and mortality. Rapid recovery of the blocked coronary flow represents the most effective strategy to reduce the size of myocardial infarction and improve the cardiac function. The aim of the study is to investigate the effects of curcumin in attenuates myocardial ischemia and reperfusion-induced proinflammatory response through activation of the Nrf-2/HO-1 signaling pathway. Wild‐type C57BL/6J mice (male, 8–10 weeks old) were used and murine myocardial ischemia and reperfusion injury (IRI) model was conducted, cardiac function was evaluated by echocardiography. Infarct size measurement, cardiac troponin-I assays, oxidative stress analysis and histopathological analyzed. The resulted data showed that curcumin alleviates myocardial inflammatory responses and oxidative stress during myocardial IRI. Also, curcumin reduces cell apoptosis induced by myocardial IRI, curcumin reduces cell apoptosis induced by myocardial IRI and activates the Nrf-2/HO-1 signaling pathway during myocardial. Inconclusion, this study demonstrates that curcumin attenuates myocardial IRI by inhibiting proinflammatory cytokines through a mechanism that may be related to activation of the Nrf-2/HO-1 signaling pathway.

Cerebral Autoregulation and Cardiovascular Physiology Dysfunction in Traumatic Brain Injury Cases: A Brief Review

Introduction: Traumatic brain injury (TBI) is one of the leading causes of death and disability in the early years of life. Post-TBI physiological alterations vary across adult and pediatric patients and severity. This disease affects the quality of life of most people. Acute hemiparesis can cause cognitive impairments. It may also impact mood, memory, and decision-making. Furthermore, parasympathetic dysfunction and sympathetic activation appear to contribute to cardiac injury via modulation of the myocardial inflammatory response via acetylcholine receptors.
 Purpose: This review aims to explain the neuronal response and cardiac dysfunction after traumatic brain injury cases.
 Methods: The review used Pubmed and Google Scholar to search for articles on traumatic brain injury, neuronal response, and cardiac biomarkers. The articles were chosen for their language, publishing, content, exposure, and outcome. The main reference is obtained from up to 79 articles that meet the inclusion requirements.
 Results: TBI can cause localized brain injury or diffuse brain injury from physical trauma such as diffuse axonal injury or brain edema. Repeated concussions raise the likelihood of chronic neurological, cognitive, and behavioral issues. Stress-induced catecholamine surges and inflammatory mediator production in response to trauma may also endanger cardiac disturbances. ECG changes in patients with severe traumatic brain injury are associated with cardiac dysfunction. Cardiac enzymes can be used as a diagnostic tool and indicate the patient's prognosis.
 Conclusion: Cerebral autoregulation and cardiac physiological responses have a synergistic relationship in maintaining tissue homeostasis in patients with traumatic brain injury. Patients with TBI may experience cardiac dysfunction as a result of the body’s exaggerated systemic response to brain injury.

Myocardial injury and inflammatory response in percutaneous device closures of pediatric patent ductus arteriosus

BackgroundThe percutaneous device closure of patent ductus arteriosus (PDA) is widely used in clinical practice, however full data on the changes in myocardial injury and systemic inflammatory markers’ levels after PDA in children are not fully reported.MethodsWe have conducted a retrospective analysis of the medical records of 385 pediatric patients in our hospital from January 2017 to December 2019. The patients were distributed into five groups. The first four (A, B, C and D) included patients divided by the type of the surgical closure methods, namely ligation, clamping, ligation-combined suturing and ligation-combined clamping, respectively. The fifth group E comprised of percutaneous device PDA patients. All recorded medical and trial data from the five groups were statistically studied.ResultsNo serious complications in the patients regardless of the classification group were reported. Our results suggested that there were no considerable differences between the groups at the baseline (with all P > 0.05). Group E demonstrated a significantly smaller operative time (42.39 ± 3.88, min) and length of hospital stay (LOS) (4.49 ± 0.50, day), less intraoperative blood loss (7.12 ± 2.09, ml) while on the other hand, a higher total hospital cost (24,001.35 ± 1152.80, RMB) than the other four groups (with all P < 0.001). Interestingly, the comparison of the inflammatory factors such as white blood cells (WBC) count, C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), as well as the myocardial injury markers (CKMB and troponin I) did not show a significant increase (P > 0.05) among the four groups. On the contrary, when the aforementioned factors and markers of all the surgical groups were compared to those in group E, we observed significantly higher speed and magnitude of changes in group E than those in groups A, B, C, and D (with all P < 0.001).ConclusionAlthough the percutaneous device closure of PDA is more comforting and drives fast recuperation in comparison to conventional surgery, it provokes myocardial injury and overall inflammation. Timely substantial and aggressive intervention measures such as the use of antibiotics before operation and active glucocorticoids to suppress inflammation and nourish the myocardium need be applied if the myocardial and inflammatory markers are eminent.

Isoliquiritigenin Ameliorates Ischemia-Induced Myocardial Injury via Modulating the Nrf2/HO-1 Pathway in Mice.

BackgroundOxidative stress and inflammatory reaction play critical roles in acute myocardial infarction (AMI). Isoliquiritigenin (ISL), a flavonoid monomer extracted from licorice, has been found to have antioxidant and anti-inflammatory effects in cancer studies. Here, we tested the effect and underlying mechanisms of ISL on ischemia-induced myocardial injury in a mouse AMI model.MethodsAdult C57BL/6 mice were pre-treated by intraperitoneal injection of ISL and/or a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 for 3 days, respectively. Then, the AMI model was established by ligating the anterior descending branch of the left coronary artery. Myocardial oxidative stress status, inflammatory response, cardiac function and infarction size were assessed after 7th day of surgery.ResultsCompared with sham group, the reactive oxygen species (ROS) and malondialdehyde (MDA) level in AMI group were significantly increased. However, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) level were dramatically decreased. ISL treatment significantly reduced the myocardial infarction area, improved cardiac function, inhibited the production of ROS and MDA and reduced the consumption of SOD and GSH-Px. Interestingly, ISL could significantly increase nuclear Nrf2 and cytosolic heme oxygenase 1 (HO-1) level in the infarcted myocardium and reduce the oxidative stress after AMI. Also, ISL treatment dramatically inhibited the activation of myocardial NF-κB pathway and reduced the expression of pro-inflammatory factors in the AMI group. However, the administration of ML385 not only suppressed the Nrf2/HO-1 activation, the anti-oxidant and anti-inflammatory effects induced by ISL, but also attenuated the beneficial role of ISL on reducing infarct size and improving cardiac function in the mouse with AMI.ConclusionThe results suggested that activation of Nrf2/HO-1 pathway has an essential role in ISL-induced cardiac protection by alleviating myocardial oxidative stress and inflammation response in mice with AMI.

Paracrine signal emanating from stressed cardiomyocytes aggravates inflammatory microenvironment in diabetic cardiomyopathy

SummaryMyocardial inflammation contributes to cardiomyopathy in diabetic patients through incompletely defined underlying mechanisms. In both human and time-course experimental samples, diabetic hearts exhibited abnormal ER, with a maladaptive shift over time in rodents. Furthermore, as a cardiac ER dysfunction model, mice with cardiac-specific p21-activated kinase 2 (PAK2) deletion exhibited heightened myocardial inflammatory response in diabetes. Mechanistically, maladaptive ER stress-induced CCAAT/enhancer-binding protein homologous protein (CHOP) is a novel transcriptional regulator of cardiac high-mobility group box-1 (HMGB1). Cardiac stress-induced release of HMGB1 facilitates M1 macrophage polarization, aggravating myocardial inflammation. Therapeutically, sequestering the extracellular HMGB1 using glycyrrhizin conferred cardioprotection through its anti-inflammatory action. Our findings also indicated that an intact cardiac ER function and protective effects of the antidiabetic drug interdependently attenuated the cardiac inflammation-induced dysfunction. Collectively, we introduce an ER stress-mediated cardiomyocyte-macrophage link, altering the macrophage response, thereby providing insight into therapeutic prospects for diabetes-associated cardiac dysfunction.

Depletion of microRNA-92a Enhances the Role of Sevoflurane Treatment in Reducing Myocardial Ischemia-Reperfusion Injury by Upregulating KLF4.

As some articles have highlighted the role of microRNA-92a (miR-92a) in myocardial ischemia-reperfusion injury (MI/RI), this article aimed to investigate the effect of miR-92a on Sevoflurane (Sevo)-treated MI/RI via regulation of Krüppel-like factor 4 (KLF4). An MI/RI rat model was established by ligating the left anterior descending coronary artery. The cardiac function, pathological changes of myocardial tissues, inflammatory response, oxidative stress and cardiomyocyte apoptosis in MI/RI rats were determined. KLF4 and miR-92a expression was detected in the myocardial tissue of rats, and the target relationship between miR-92a and KLF4 was confirmed. Sevo treatment alleviated myocardial damage, inflammatory response, oxidative stress response, and cardiomyocyte apoptosis, and improved cardiac function in MI/RI rats. miR-92a increased and KLF4 decreased in the myocardial tissue of MI/RI rats. KLF4 was targeted by miR-92a. Downregulation of miR-92a or upregulation of KLF4 further enhanced the effect of Sevo treatment on MI/RI. This study suggests that depletion of miR-92a promotes upregulation of KLF4 to improve cardiac function, reduce cardiomyocyte apoptosis and further enhance the role of Sevo treatment in alleviating MI/RI.

Evaluation of low-dose colchicine in patients with cardiopulmonary bypass: study protocol for a randomised controlled trial

IntroductionInflammation and myocardial damage caused by cardiovascular surgery with cardiopulmonary bypass (CPB) have been shown to be the major contributors to postoperative morbidity and mortality. Colchicine can reduce myocardial ischaemia-reperfusion...

Clinical Efficacy of Subhypothermia in the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy Combined with Myocardial Damage

Objective. To investigate the efficacy of subhypothermia in the treatment of neonatal hypoxic-ischemic encephalopathy (HIE) combined with myocardial damage. Methods. 136 children with HIE and myocardial damage admitted to our hospital from October 2019 to October 2021 were included in the study and were divided into study group and control group of 68 cases each according to the random number table method. The control group was given conventional treatment, and the study group was treated with subhypothermia therapy on top of the control group. Comparing the effects of treatment between the two groups. The serum levels of S-100 β protein, Tau protein, neuron-specific enolase (NSE), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase ( ɑ-HBDH), myoglobin (Myo), cardiac trophic factor-1 (CT-1), cardiac troponin I (cTnI), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), interleukin-1 β (IL-1 β), interleukin-8 (IL-8), and tumor necrosis factor- ɑ (TNF- ɑ) were measured in both groups before and after treatment, respectively. Results. The total effective rate was higher in the study group (88.24%) than in the control group (72.06%) ([Formula: see text]). After treatment, the serum levels of S-100 β protein, Tau protein, NSE, CK, CK-MB, LDH, ɑ-HBDH, Myo, CT-1, cTnI, ROS, IL-1 β, IL-8, and TNF- ɑ were reduced in both groups, and the study group was lower than the control group ([Formula: see text]). The serum levels of SOD and GSH-Px were higher in both groups after treatment than before treatment and were higher in the study group than in the control group ([Formula: see text]). Conclusion. Subhypothermia treatment of children with HIE combined with myocardial injury can further improve the hypoxic-ischemic state; reduce myocardial damage, oxidative stress, and inflammatory response; and has a good overall efficacy.

Nrf2 Promotes Inflammation in Early Myocardial Ischemia-Reperfusion via Recruitment and Activation of Macrophages.

Cardiomyocyte apoptosis in response to inflammation is a primary cause of myocardial ischemia-reperfusion injury (IRI). Nuclear factor erythroid 2 like 2 (Nrf2) reportedly plays an important role in myocardial IRI, but the underlying mechanism remains obscure. Expression data from the normal heart tissues of mice or heart tissues treated with reperfusion for 6 h after ischemia (IR6h) were acquired from the GEO database; changes in biological function and infiltrating immune cells were analyzed. The binding between the molecules was verified by chromatin immunoprecipitation sequencing. Based on confirmation that early myocardial ischemia-reperfusion (myocardial ischemia/reperfusion for 6 hours, IR6h) promoted myocardial apoptosis and inflammatory response, we found that Nrf2, cooperating with Programmed Cell Death 4, promoted transcription initiation of C-C Motif Chemokine Ligand 3 (Ccl3) in myocardial tissues of mice treated with IR6h. Moreover, Ccl3 contributed to the high signature score of C-C motif chemokine receptor 1 (Ccr1)-positive macrophages. The high signature score of Ccr1-positive macrophages leads to the release of pro-inflammatory factors interleukin 1 beta and interleukin 6. This study is the first to elucidate the damaging effect of Nrf2 via remodeling of the immune microenvironment in early myocardial ischemia-reperfusion, which provides us with new perspectives and treatment strategies for myocardial ischemia-reperfusion.