Myocardial Infarction Area Research Articles

Inhibiting H2AX Can Ameliorate Myocardial Ischemia/Reperfusion Injury by Regulating P53/JNK Signaling Pathway.

Myocardial ischemia-reperfusion (I/R) injury is a significant area of focus in cardiovascular disease research. I/R injury can increase intracellular oxidative stress, leading to DNA damage. H2AX plays a crucial role in DNA repair. This study utilized mouse and cell models of myocardial I/R to investigate the impact of H2AX on cardiomyocytes during I/R. This study initially assessed the expression of H2AX in MI/R mice compared to a sham surgery group. Subsequently, cardiac function, infarct area, and mitochondrial damage were evaluated after inhibiting H2AX in MI/R mice and a negative control group. Furthermore, the study delved into the molecular mechanisms by analyzing the expression of H2AX, P53, p-JNK, SHP2, p-SHP2, p-RAS, parkin, Drp1, Cyt-C, Caspase-3, and Caspase-8 in cardiomyocytes following the addition of JNK or P53 agonists. The results from western blotting in vivo indicated significantly higher H2AX expression in the MI/R group compared to the sham group. Inhibiting H2AX improved cardiac function, reduced myocardial infarct area, and mitigated mitochondrial damage in the MI/R group. In vitro experiments demonstrated that inhibiting H2AX could attenuate mitochondrial damage and apoptosis in myocardial cells by modulating the P53 and JNK signaling pathways. These findings suggested that inhibiting H2AX may alleviate myocardial I/R injury through the regulation of the P53/JNK pathway, highlighting H2AX as a potential target for the treatment of myocardial ischemia/reperfusion injury.

Ulinastatin protects against myocardial ischemia/reperfusion injury in rats via Rho/ROCK signaling pathway.

We aimed to study the influences of ulinastatin on diseased myocardial tissues, cardiomyocyte apoptosis and inflammatory reaction in rats with myocardial ischemia/reperfusion injury (IRI) via the Ras homolog (Rho)/Rho-associated kinase (ROCK) signaling pathway and its mechanism. The rats were randomly divided into three groups: control group (C group), IR model group (IR group) and IR model + ulinastatin treatment group (UR group). The pathological changes in myocardial tissues were detected via HE staining, the markers of myocardial injury were examined using kits, and apoptosis was determined through TUNEL assay. Moreover, ELISA was applied to measure the expressions of TNF-α, interleukin-6 (IL-6) and IL-8 in cardiac tissues, and Western blotting was performed to detect the protein expression levels of RhoA, ROCK2 and MLCP. The myocardial infarction area in the IR group was markedly larger than that in the C group (P<0.01) but was significantly reduced after ulinastatin treatment (P<0.05), and the IR group had higher levels of AST, cTnI, CK-MB and LDH than C group, but the levels of those indexes were significantly reduced after ulinastatin treatment.The cardiomyocyte apoptosis was increased in the IR group compared with that in the C group, while it was decreased in the UR group in comparison with that in the IR group. Besides, the UR group exhibited lowered expression levels of the Rho/ROCK signaling pathway-related proteins compared with the IR group. Ulinastatin may ameliorate the prognosis of rats with myocardial IRI via the Rho/ROCK signaling pathway.

Melatonin reduces myocardial cell damage in myocardial ischemia/reperfusion rats by inhibiting NLRP3 activation.

Melatonin (Mel) is an endogenous hormone with many pharmacological effects, such as sedation, hypnosis, antidepressant, blood pressure regulation, anti-inflammatory and anti-tumor. It is mainly synthesized by pineal gland in vivo. Mel can regulate the function of cardiovascular system and effectively reduce myocardial cell injury, thus playing a role in myocardial protection, but its specific mechanism is unclear. Ischemia-reperfusion injury (IRI) often leads to poor prognosis and complications in patients with cardiovascular diseases, and inflammatory reaction mediated by nod-like receptor thermoprotein domain-related protein 3(NLRP3) is an important reason for the further aggravation of subsequent injury after IRI. Rats were intervened with Mel or NLRP3 inhibitor MCC950 for 10 days, and then the IRI rat model was established. After that, rats were anesthetized and killed, and myocardial tissues were collected for experiments. The experimental results showed that Mel reduced the myocardial infarction area, decreased aspartate aminotransferase (AST), creatine kinase myocardial band (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA), and significantly inhibited the expression of reactive oxygen species (ROS), NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC), but its effect on superoxide dismutase (SOD) was opposite. Therefore, Melmay improve autophagy and inflammation during myocardial ischemia/reperfusion and may decrease myocardial cell damage by inhibitingNLRP3.

Shuxuening Injection Inhibits Apoptosis and Reduces Myocardial Ischemia-Reperfusion Injury in Rats through PI3K/AKT Pathway.

To investigate the main components and potential mechanism of Shuxuening Injection (SXNI) in the treatment of myocardial ischemia-reperfusion injury (MIRI) through network pharmacology and in vivo research. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose (3.68 mg/kg), medium-dose (7.35 mg/kg), and high-dose (14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group (14.7 mg/kg), SXNI+LY294002 group, and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride (TTC) double staining, hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) pathway was closely related to SXNI treatment of MIRI. In vivo experiments showed that SXNI reduced the myocardial infarction area in the model group, improved rat heart pathological damage, and reduced the cardiomyocyte apoptosis rate (all P<0.01). After SXNI treatment, the p-PI3K/PI3K and p-AKT/AKT ratios as well as B-cell lymphoma-2 (Bcl-2) protein expression in cardiomyocytes were increased, while the Bax and cleaved caspase 3 protein expression levels were decreased (all P<0.05). LY294002 partially reversed the protective effect of SXNI on MIRI. SXNI protects against MIRI by activating the PI3K/AKT signaling pathway.

Exploring the role and mechanism of hyperoside against cardiomyocyte injury in mice with myocardial infarction based on JAK2/STAT3 signaling pathway

BackgroundMyocardial infarction (MI) is one of the most deadly diseases in the world. Hyperoside (Hyp) has been shown to have a protective effect on cardiovascular function through various signaling pathways, but whether it can protect myocardial infarction by regulating JAK2/STAT3 signaling pathway is unknown. Aim of the studyTo investigate whether Hyp could protect the heart against myocardial infarction injury in mice by modulating JAK2/STAT3 signaling pathway and its potential mechanism. MethodsIn vivo experiments, the myocardial infarction model was established by ligating the left anterior descending coronary artery (LAD) of male C57BL/6 mice permanently. The mice were divided into seven groups: sham group, MI group, MI+Hyp (9 mg/kg), MI+Hyp (18 mg/kg) group, MI+Hyp (36 mg/kg) group, MI+Captopril group (15 mg/kg) group and MI+Hyp (36 mg/kg)+AG490 (7.5 mg/kg) group. Each group of animals were given different concentrations of hyperoside, positive control drug or inhibitor of JAK2/STAT3 singaling. After 14 days of administration, the electrocardiogram (ECG), echocardiography and serum myocardial injury markers were examined; Slices of mouse myocardial tissue were assessed for histopathological changes by HE, Masson and Sirius Red staining. TTC and TUNEL staining were used to evaluate the myocardial infarction area and cardiomyocytes apoptosis respectively. The expression of JAK2/STAT3 signaling pathway, apoptosis and autophagy-related proteins were detected by western blot. In vitro experiments, rat H9c2 cardiomyocytes were deprived of oxygen and glucose (OGD) to stimulate myocardial ischemia. The experiment was divided into seven groups: Control group, OGD group, OGD+Hyp (20 μM) group, OGD+Hyp (40 μM) group, OGD+Hyp (80 μM), OGD+Captopril (10 μM) group and OGD+Hyp (80 μM)+AG490 (100 μM) group. Myocardial cell damage and redox index were measured 12 h after OGD treatment. ROS content in cardiomyocytes was detected by immunofluorescence. Cardiomyocytes apoptosis was detected by flow cytometry. The expressions of JAK2/STAT3 signaling pathway-related proteins, apoptosis and autophagy related proteins were detected by western blot. ResultsIn vivo, hyperoside could ameolirate ECG abnormality, increase cardiac function, reduce myocardial infarction size and significantly reduce myocardial fibrosis level and oxidation level. The experimental results in vitro showed that Hyp could reduce the ROS content in cardiomyocytes, decrease the level of oxidative stress and counteract the apoptosis induced by OGD injury . Both in vivo and in vitro experiments showed that hyperoside could increase phosphorylated JAK2 and STAT3, indicating that hyperoside could play a cardioprotective role by activating JAK2/STAT3 signaling pathway. It was also shown that hyperoside could increase the autophagy level of cardiomyocytes in vivo and in vitro. However the cardiomyocyte-protective effect of Hyp was abolished in combination with JAK2/ STAT3 signaling pathway inhibitor AG490. These results indicated that the protective effect of Hyp on cardiomyocyte injury was at least partially achieved through the activation of the JAK2/STAT3 signaling pathway. ConclusionHyp can significantly improve cardiac function, ameliorate myocardial hypertrophy and myocardial remodeling in MI mice. The mechanism may be related to improving mitochondrial autophagy of cardiomyocytes to maintain the advantage of autophagy, and blocking apoptosis pathway through phagocytosis, thus suppressing apoptosis level of cardiomyocytes. These effects of Hyp are achieved, at least in part, by activating the JAK2/STAT3 signaling pathway.

Effect and mechanism of Poria cocos polysaccharides on myocardial cell apoptosis in rats with myocardial ischemia-reperfusion injury by regulating Rho-ROCK signaling pathway

This study aimed to investigate the effect and underlying mechanism of Poria cocos polysaccharides(PCP) on myocardial cell apoptosis in the rat model of myocardial ischemia-reperfusion injury(MI/RI). Male SPF-grade SD rats were randomly divided into a sham group(saline), a model group(saline), low-and high-dose PCP groups(100 and 200 mg·kg~(-1)), and a fasudil group(10 mg·kg~(-1)), with 16 rats in each group. Except for the sham group, the other four groups underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion for 2 h to establish the MI/RI model. The myocardial infarct area was assessed by TTC staining. Histological changes were observed through HE staining. Myocardial cell apoptosis was evaluated using TUNEL staining. Serum lactate dehydrogenase(LDH), creatine kinase MB(CK-MB), interleukin-1β(IL-1β) and IL-18 levels, myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were detected by ELISA. Protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved caspase-3, Ras homolog gene A(RhoA), myosin phosphatase target subunit 1(MYPT-1), phosphorylated MYPT-1(p-MYPT-1), and Rho-associated coiled-coil forming kinase 1(ROCK 1) were measured by Western blot. Pathological staining of myocardial tissue revealed that in the model group, there was focal necrosis of myocardial tissue, myocardial cell swelling, unclear boundaries, and neutrophil infiltration. These pathological changes were alleviated in the low-and high-dose PCP groups and the fasudil group. Compared with the model group, the low-and high-dose PCP groups and the fasudil group showed significantly reduced myocardial infarct area and myocardial cell apoptosis rate. Compared with the sham group, the model group exhibited elevated serum LDH, CK-MB, IL-1β and IL-18 levels, increased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and decreased myocardial SOD levels and Bcl-2 protein expression. Compared with the model group, the PCP groups and the fasudil group showed lowered serum LDH, CK-MB, IL-1β and IL-18 levels, decreased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and increased myocardial SOD levels and Bcl-2 protein expression. PCP exhibited a certain preventive effect on myocardial tissue pathological damage and myocardial cell apoptosis in MI/RI rats, possibly related to the inhibition of the Rho-ROCK signaling pathway activation, thereby reducing oxidative stress and inflammatory responses.

Resveratrol Inhibited Nanoparticles Stromal Interaction Molecule 2 in Regulating miR-20b-5p Signaling Pathway to Improve Mitochondrial Function During Myocardial Ischemia-Reperfusion Injury

Myocardial ischemia-reperfusion (IR) in diabetes can cause severe myocardial damages. In this study, resveratrol (RES) nanoparticles were used in diabetic myocardial IR rat model injury to assess its effect on mitochondria function. Rat models were assigned into sham group, IR group, IR+RES group, IR+RES+mir-NC group, and IR+RES+miR-20b-5p inhibitor group. Myocardial infarction area was measured by TTC in 5 rats from each group, and ultrasound was used to detect left ventricular end-systolic internal diameters (LVIDs) and end-diastolic internal diameters (LVIDd), along with analysis of cardiomyopathy by HE staining. miR-20b-5p and Stromal interaction molecule 2 (STIM2) expressions, cardiomyocyte proliferation, apoptosis, cell viability, mitochondrial function, and relationship between miR-20b-5p and STIM2 were also analyzed. Resveratrol (RES) nanoparticles were prepared successfully. Myocardial infarct size, LVIDd and LVIDs of rats in IR+RES group decreased (vs. IR group), but were higher than sham group. miR-20b-5p expression also increased in the IR+RES group (vs. IR group), and the above indicators were decreased by the miR-20b-5p inhibitor (vs. IR+RES group, P &lt;0.05). The myocardial changes in rats from the IR+RES+miR-20b-5p antagomir group were smaller (vs. IR group), while STIM2 expression was lower than in the IR group after using the RES nanoparticles (P &lt; 0.05). RES nanoparticles can thus enhance mitochondrial function and cell viability of cardiomyocytes, increasing cell proliferation rate and decreasing apoptosis rate (vs. IR group,P &lt;0.05). After using the RES nanoparticles to interfere with myocardial IR in the diabetic rats, they were found to inhibit STIM2 and improve mitochondria by regulating miR-20b-5p signaling pathway.

Baseline risk, time window, and indications for delayed percutaneous coronary interventions, their significance in treatment of ST-segment elevation myocardial infarction

The aim of the study was to estimate the significance of delayed percutaneous coronary interventions (PCIs) in the treatment of ST-segment elevation myocardial infarction (STEMI), to weigh the initial mortality risk (MR) while determining the indications for their use and the time window for the use of mechanical reperfusion in late hospital admission. Total 2226 patients admitted to the Institute with STEMI for the period 2008–2017 were studied. Emergency coronary angiography was performed in 945 admitted patients in the initial 12 hours and in 834 patients after 12–72 hours of STEMI onset; PCI was performed in 784 and 619 patients, respectively. In all patients, MR was scored by TIMI; angiographic success was assessed as TIMI 3 coronary flow and compared to ECG signs of reperfusion. The baseline MR score averaged 5 or 12.5%, being corresponded to score 4.2 or 8% in patients with PCI performed in the initial 12 hours, score 5 or 12.5% in those with PCI performed after 12–72 hours, and score 6 or 16% in patients without PCI; or with respect to the patient age, MR scored 3.7 or 7%, 6 or 16%, and 7.5 or 25%, for those under the age of 65 years, those from 65–75 years, and those over 75 years old, respectively. Mortality in patients with an early and delayed PCI was 5.2% and 4.2%, respectively, and 15.6% in patients without PCI; after patient distribution by age under 65, 65–75, and over 75 years old, the respective mortality rates were 3.8%, 4.9%, and 10.8% after an early PCI; 2.6%, 5.8%, and 8.2% after a delayed PCI; and 8.4%, 19.4%, and 28% among those without PCI. For 10 years, the number of primary PCIs had increased from 39% to 78%. The ratio of early to delayed PCI made 56% to 44%. Of 195 deaths (67 patients with PCI and 128 without PCI), 90% of patients had a three-vessel disease; 83% of patients had the MI area over 30%; and the cause of death in 84% was pulmonary edema. The presented data suggest a high practical significance of delayed PCI in patients with initially high MR, its most weighty components being the age over 75 years and severe manifestations of acute heart failure (AHF). Unlike early PCIs, the delayed PCIs are used less frequently, the initial MR is not taken into account, and they are abstained from in respect to people over 75 years of age. The reduction in mortality, proportional to the baseline MR, suggests their correlation to PCI results and the feasibility of PCI use without age restrictions. The use of primary PCIs in late hospital admissions, by analogy with early ones or selectively in high MR, will help to optimize the treatment tactics and minimize mortality.

Sugarcane leaf polysaccharide exerts a therapeutic effect on cardiovascular diseases through necroptosis

BackgroundNecroptosis, a novel form of programmed cell death wherein the necrotic morphology is characterized by swelling of the cells, rupture of the plasma membrane, and dysfunction of the organelle, has been always observed in cardiovascular diseases. Sugarcane leaf polysaccharide (SLP) are primary components present in sugarcane leaves that exert cardiovascular protective effects. However, the positive effect of SLP and underlying mechanisms in myocardial ischemia-reperfusion (MI/R) remain unexplored. AimIn this study, the protective effects of SLP on MI/R injury were investigated under in vitro and in vivo conditions. MethodsThe protective effects of SLP on MI/R injury were assessed using tertiary butyl hydrogen peroxide (TBHP)–stimulated-H9c2 cells in the in vitro assay and using Sprague Dawley rats in the in vivo assay. ResultsIn vitro, SLP significantly reversed TBHP-induced H9c2 cell death by inhibiting necroptosis and oxidative stress. SLP exerted antioxidant activity through the Nrf2/HO-1 pathway. SLP suppressed necroptosis by decreasing phosphorylation of RIP1, RIP3, and MLKL in TBHP-stimulated H9c2 cells. In vivo, SLP attenuated MI/R injury by decreasing the myocardial infarct area; increasing myeloperoxidase and superoxide dismutase levels; and reducing malondialdehyde, interleukin-6, and tumor necrosis factor-α levels.

Effect of miR-182-5p on apoptosis in myocardial infarction

ObjectiveThis study aimed to delineate the diagnostic significance of miR-182-5p by investigating its influence on myocardial apoptosis and function, employing both in vivo and in vitro myocardial infarction models. MethodsA rat myocardial infarction model was established. Myocardial infarction area was detected using the 2,3,5-chlorotriphenyltetrazolium (TTC) method, myocardial enzyme spectrums were measured using enzyme-linked immunosorbent assay (ELISA), myocardial structure was detected by hematoxylin and eosin (HE) staining, myocardial apoptosis was detected using the TUNEL method, and expression levels of miR-182-5p and apoptosis-related molecules were detected using real-time fluorescence quantitative PCR (qPCR) and Western blot. miR-182-5p mimics and inhibitor were transfected into rat H9C2 cardiomyocytes and mouse HL-1 cardiomyocytes to establish a hypoxia model. Cardiomyocyte viability was detected using the CCK-8 method, expression levels of apoptosis-related indicators were detected using Western blot, and caspase-3/7 activity was detected using a caspase-3/7 activity detection kit. AAV9 adeno-associated virus was used to construct an miR-182-5p overexpression virus, which was injected into mice through the tail vein to create a mouse myocardial infarction model. TTC, ELISA, HE staining, echocardiography, real-time fluorescence qPCR, and Western blot methods were used to detect the effects of AAV9-miR-182-5p on myocardial injury, myocardial function, and myocardial apoptosis levels in myocardial infarction. ResultsThe rat model displayed reduced miR-182-5p expression concurrent with an increase in apoptosis. The in vitro H9C2 and HL-1 hypoxia models revealed that miR-182-5p augmented the hypoxia-induced decrease in myocardial cell viability, suppressed Bcl-2 expression, and increased Bax, Bnip3, and caspase-3/7 activity levels. The injection of AAV9-miR-182-5p significantly exacerbated myocardial tissue damage, impaired myocardial function, and enhanced apoptosis. ConclusionmiR-182-5p escalates myocardial injury during myocardial infarction by fostering apoptosis. Interventions that aim to reduce miR-182-5p levels might be crucial in halting the progression of myocardial infarction.

Automatic Myocardium Segmentation in Delayed-Enhancement MRI with Pathology-Specific Data Augmentation and Deep Learning Architectures

The extent of myocardial infarction (MI) can be evaluated thanks to delayed enhancement (DE) cardiac MRI. DE MRI is an imaging technique acquired several minutes after the injection of a contrast agent where MI appears with a bright signal. The automatic myocardium segmentation in DE MRI is quite challenging, especially when MI is present, since these areas usually showcase a heterogeneous aspect in terms of shape and intensity, thus obstructing the myocardium visibility. To overcome this issue, we propose an image processing-based data augmentation algorithm where diverse synthetic cases of MI were created in two different ways: fixed and adaptive. In the first one, the training set is enlarged by a specific factor, whereas in the second, the method receives feedback from the segmentation model during training and performs the augmentation exclusively on complex cases. The method performance was evaluated in single and multi-modality settings. In this latter, information from kinetic images (Cine MRI), which are acquired along DE MRI in the same examination, is also used, and the extracted features from both modalities are fused. The results show that applying the data augmentation in a fixed fashion on a multi-modality setting leads to a more consistent segmentation of the myocardium in DE MRI. The segmentation models, which were all UNet-based architectures, can better relate MI areas with the myocardium, thus increasing its overall robustness to pathology-specific local pattern perturbations.

The effect of ticagrelor on myocardial microcirculation, cardiac function, and adverse cardiovascular events in STEMI patients after PCI.

This study aimed to investigate the effects of ticagrelor on myocardial microcirculation, cardiac function, and adverse cardiovascular events in ST-segment elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). A total of 80 STEMI patients admitted to our hospital from February 2020 to March 2023 were selected and included in the retrospective study, all receiving PCI treatment. They were randomly and retrospectively divided into a control group (40 cases) and an observation group (40 cases), and treated with clopidogrel and ticagrelor, respectively. The clinical effects were compared. The starting perfusion time of the contrast agent in the myocardial infarction area in the observation group was 2.22±0.27 s, and the peak perfusion time was 2.62±0.27 s, which was lower than those in the control group (2.51±0.29 s and 3.21±0.39 s, t=4.629, 7.867, p=0.000). The ratio of peak perfusion intensity between the two groups was significantly different (t=2.363, p=0.021). Left ventricular ejection fraction, stroke volume index, and cardiac index in the observation group were higher than those in the control group (55.03±6.03 vs. 52.33±5.13; 57.39±6.81 vs. 51.11±6.31 L/min·m-2; 3.49±0.45 vs. 3.12±0.38 mL/m2, t=2.157, 4.278, 3.973, p<0.05). The observation group had lower levels of brain natriuretic peptide and C-reactive protein compared to the control group (425.35±55.71 vs. 589.36±70.24 pg/mL; 15.13±1.03 vs. 21.64±2.74 mg/L; t=11.570, 14.066, p=0.000). There was no statistical significance in the incidence of adverse cardiovascular events between the two groups (2.50% vs. 7.50%, χ2=1.920, p=0.166). The use of ticagrelor can regulate myocardial microcirculation and improve cardiac function in STEMI patients undergoing PCI.

Protective effect of luteolin on cardiac ischemia/reperfusion injury in rats with myocardial infarction through ERK/JNK signaling pathway

Due to the increased incidence of cardiovascular diseases, the incidence of cardiac ischemia/reperfusion injury (IRI) is also on the rise. Luteolin has a certain protective effect on myocardium. Therefore, this study focuses on whether luteolin can protect IRI in rats with myocardial infarction. A myocardial infarction rat model was prepared and the isolated heart was treated to induce cardiac ischemia-reperfusion injury. British biodegradable packaging company (BIOPAC) biological signal collector detects myocardial indicators; semi-automatic biochemical analyzer detects myocardial infarct size; hematoxylin-eosin (HE) staining observes pathological changes along with analysis of the levels of ERK, JNK, and Caspase-3 and proliferation and apoptosis of myocardial cells. Luteolin can improve the myocardial index level of rats with myocardial infarction and increase survival rate; the rats in luteolin group have the smallest myocardial infarction area, and the myocardial tissue is tightly arranged, the myocardial collagen is significantly reduced, and the myocardial injury index is significantly reduced. Luteolin inhibited the proliferation, migration and apoptosis of cardiomyocytes. Caspase-3, ERK, and JNK expression in the ERK/JNK agonist group was the most obvious. Their levels were highest in the luteolin+ERK/JNK agonist group (vs. other groups, P &lt;0.05), which was higher than ERK/JNK agonist group. Luteolin can inhibit Caspase-3 expression by activating ERK/JNK signaling pathway, thereby reducing myocardial injury.

CFLIPL alleviates myocardial ischemia-reperfusion injury by regulating pyroptosis.

Alleviating myocardial ischemia-reperfusion injury (MIRI) plays a critical role in the prognosis and improvement of cardiac function following acute myocardial infarction. Pyroptosis is a newly identified form of cell death that has been implicated in the regulation of MIRI. In our study, H9c2 cells and SD rats were transfected using a recombinant adenovirus vector carrying cFLIPL , and the transfection was conducted for 3 days. Subsequently, H9c2 cells were subjected to 4 h of hypoxia followed by 12 h of reoxygenation to simulate an in vitro ischemia-reperfusion model. SD rats underwent 30 min of ischemia followed by 2 h of reperfusion to establish an MIRI model. Our findings revealed a notable decrease in cFLIPL expression in response to ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) injuries. Overexpression of cFLIPL can inhibit pyroptosis, reducing myocardial infarction area in vivo, and enhancing H9c2 cell viability in vitro. I/R and H/R injuries induced the upregulation of ASC, cleaved Caspase 1, NLRP3, GSDMD-N, IL-1β, and IL-18 proteins, promoting cell apoptosis. Our research indicates that cFLIPL may suppress pyroptosis by strategically binding with Caspase 1, inhibiting the release of inflammatory cytokines and preventing cell membrane rupture. Therefore, cFLIPL could potentially serve as a promising target for alleviating MIRI by suppressing the pyroptotic pathway.

Cardiac progenitor cells-derived exosomes alleviate myocardial injury by regulating Treg cell differentiation through the mTOR pathway in mice with myocardial infarction

To investigate the effect of cardiac progenitor cells-derived exosomes (CPCs-Exo) on Treg differentiation in mice with myocardial infarction (MI). Mouse models of MI established by ligation of the left anterior descending coronary artery (LAD) were treated with CPCs-Exos, and naive CD4+T cells were isolated from the spleen of the mice and divided into control group, CD4+T cell activation group (CD3+CD28), CPCs-Exos stimulation group (CD3+CD28+CPCs-Exos), mTOR activator group (CD3+CD28+CPCs-Exos+mTOR activator) and mTOR inhibitor group (CD3+CD28+CPCs-Exos+mTOR inhibitor). Western blotting was used to detect the expression levels of mTOR and p-mTOR in the treated cells. Flow cytometry was used to analyze the percentages of Treg and CD4+IL-10+T cells. The infarct size of the mice were measured with 2, 3, 5-triphenyltetrazole chloride (TTC) staining, and serum levels of LDH and CK-MB were detected using an automatic biochemical analyzer. Compared with the control group, the mouse models of MI showed significantly increased release of LDH (P<0.001) and CK-MB (P=0.0002) and increased percentages of Treg and CD4+IL-10+T cells. Treatment with CPC-Exos effectively reduced the MI area and lowered serum levels of LDH (P=0.003) and CK-MB (P=0.003) and the percentages of Tregs (P=0.001) and CD4+IL-10+T cells (P=0.004) in the MI mouse models. In the isolated CD4+T cells, CPCsExos treatment significantly up-regulated the percentages of Treg (P=0.01) and CD4+IL-10+ T cells (P=0.004) and increased the expression of mTOR (P=0.009) and p-mTOR (P=0.009), and these effects could be further enhanced by the mTOR activator but obviously attenuated by the mTOR inhibitor. CPCs-Exos promotes the differentiation of Treg in mice with MI by modulating the mTOR signaling pathway.

Irisin ameliorates myocardial ischemia-reperfusion injury by modulating gut microbiota and intestinal permeability in rats.

Recently, myocardial ischemia-reperfusion (I/R) injury was suggested associated with intestinal flora. However, irisin has demonstrated beneficial effects on myocardial I/R injury, thus increasing interest in exploring its mechanism. Therefore, whether irisin interferes in gut microbiota and gut mucosal barrier during myocardial I/R injury was investigated in the present study. Irisin was found to reduce the infiltration of inflammatory cells and fracture in myocardial tissue, myocardial enzyme levels, and the myocardial infarction (MI) area. In addition, the data showed that irisin reverses I/R-induced gut dysbiosis as indicated by the decreased abundance of Actinobacteriota and the increased abundance of Firmicutes, and maintains intestinal barrier integrity, reduces metabolic endotoxemia, and inhibits the production of proinflammatory cytokines interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). Based on the results, irisin could be a good candidate for ameliorating myocardial I/R injury and associated diseases by alleviating gut dysbiosis, endothelial dysfunction and anti-inflammatory properties.

Electroacupuncture preconditioning protects against myocardial ischemia-reperfusion injury by modulating dynamic inflammatory response

BackgroundThe protective effects of electroacupuncture (EA) preconditioning against myocardial ischemia-reperfusion injury (MIRI) have been reported. However, the underlying mechanism remains unclear. Recent research has indicated that the dynamic inflammatory response following MIRI plays an essential role in the progression of myocardial injury. This study aimed to investigate the myocardial protective effects of EA preconditioning on MIRI in rats and to explore the relevant mechanism from the perspective of dynamic inflammatory response. MethodsA MIRI model was employed, and the rats were subjected to EA on Neiguan for four days prior to modeling. The myocardial protective effect of EA preconditioning was evaluated by echocardiography, Evans blue and triphenyltetrazolium chloride staining. Real-time polymerase chain reaction, Western blot, hematoxylin & eosin staining, and immunohistochemistry were utilized to detect the content of mitochondrial DNA, NOD receptor family protein 3 (NLRP3) inflammasome activation, neutrophil recruitment and macrophage infiltration in blood samples and myocardium below the ligation. ResultsWe found that EA preconditioning could accelerate the recovery of left ventricle function after MIRI and reduce the myocardial infarction area, thereby protecting the myocardium against MIRI. Furthermore, EA preconditioning was observed to ameliorate mitochondrial impairment, reduce the level of plasma mitochondrial DNA, modulate NLRP3 inflammasome activation, attenuate neutrophil infiltration, and promote the polarization of M1 macrophages towards M2 macrophages in the myocardium after MIRI. ConclusionEA preconditioning could reduce plasma mtDNA, suppress overactivation of the NLRP3 inflammasome, facilitate the transition from the acute pro-inflammatory phase to the anti-inflammatory reparative phase after MIRI, and ultimately confer cardioprotective benefits.

PDHA1 Alleviates Myocardial Ischemia-Reperfusion Injury by Improving Myocardial Insulin Resistance During Cardiopulmonary Bypass Surgery in Rats.

Cardiopulmonary bypass (CPB) is a requisite technique for thoracotomy in advanced cardiovascular surgery. However, the consequent myocardial ischemia-reperfusion injury (MIRI) is the primary culprit behind cardiac dysfunction and fatal consequences post-operation. Prior research has posited that myocardial insulin resistance (IR) plays a vital role in exacerbating the progression of MIRI. Nonetheless, the exact mechanisms underlying this phenomenon remain obscure. We constructed pyruvate dehydrogenase E1 α subunit (PDHA1) interference and overexpression rats and used ascending aorta occlusion in an in vivo model of CPB-MIRI. We devised an in vivo model of CPB-MIRI by constructing rat models with both pyruvate dehydrogenase E1α subunit (PDHA1) interference and overexpression through ascending aorta occlusion. We analyzed myocardial glucose metabolism and the degree of myocardial injury using functional monitoring, biochemical assays, and histological analysis. We discovered a clear downregulation of glucose transporter 4 (GLUT4) protein content expression in the CPB I/R model. In particular, cardiac-specific PDHA1 interference resulted in exacerbated cardiac dysfunction, significantly increased myocardial infarction area, more pronounced myocardial edema, and markedly increased cardiomyocyte apoptosis. Notably, the opposite effect was observed with PDHA1 overexpression, leading to a mitigated cardiac dysfunction and decreased incidence of myocardial infarction post-global ischemia. Mechanistically, PDHA1 plays a crucial role in regulating the protein content expression of GLUT4 on cardiomyocytes, thereby controlling the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI. Overall, our study sheds new light on the pivotal role of PDHA1 in glucose metabolism and the development of myocardial insulin resistance. Our findings hold promising therapeutic potential for addressing the deleterious effects of MIRI in patients.

Preliminary Evaluation of 18F-Labeled Benzylguanidine Analogs as NET Tracers for Myocardial Infarction Diagnosis.

Heart failure (HF) remains a major cause of late morbidity and mortality after myocardial infarction (MI). To date, no clinically established 18F-labeled sympathetic nerve PET tracers for monitoring myocardial infarction are available. Therefore, in this study, we synthesized a series of 18F-labeled benzyl guanidine analogs and evaluated their efficacy as cardiac neuronal norepinephrine transporter (NET) tracers for myocardial imaging. We also investigated the preliminary diagnostic capabilities of these tracers in myocardial infarction animal models, as well as the structure-activity relationship of these tracers. Three benzyl guanidine-NET tracers, including [18F]1, [18F]2, and [18F]3, were synthesized and evaluated in vivo as PET tracers in a myocardial infarction mouse model. [18F]LMI1195 was used as a positive control for the tracers. H&E staining of the isolated myocardial infarction heart tissue sections was performed to verify the efficacy of the selected PET tracer. Our data show that [18F]3 had a moderate decay corrected labeling yield (~10%) and high radiochemical purity (>95%) compared to other tracers. The uptake of [18F]3 in normal mouse hearts was 1.7±0.1%ID/cc at 1 h post-injection (p. i.), while it was 2.4±0.1, 2.6±0.9, and 2.1±0.4%ID/cc in the MI mouse hearts at 1, 2, and 3 days after surgery, respectively. Compared with [18F]LMI1195, [18F]3 had a better myocardial imaging effect in terms of the contrast between normal and MI hearts. The area of myocardial infarction shown by PET imaging corresponded well with the infarcted tissue demonstrated by H&E staining. With an obvious cardiac uptake contrast between normal mice and the myocardial infarction mouse model, [18F]3 appears to be a potential tool in the diagnosis of myocardial infarction. Therefore, it is necessary to conduct further structural modification studies on the chemical structure of [18F]3 to improve its in vivo stability and diagnostic detection ability to achieve reliable and practical imaging effects.

The Efficacy of Transplanting Human Umbilical Cord Mesenchymal Stem Cell Sheets in the Treatment of Myocardial Infarction in Mice.

The transplantation of mesenchymal stem cell (MSC) sheets derived from human umbilical cords (hUCs) was investigated in this study as a potential application in treating myocardial infarction (MI). Two groups of hUC-MSC sheets were formed by populating LunaGelTM, which are 3D scaffolds of photo-crosslinkable gelatin-based hydrogel with two different cell densities. An MI model was created by ligating the left anterior descending coronary artery of healthy BALB/c mice. After two weeks, the cell sheets were applied directly to the MI area and the efficacy of the treatment was evaluated over the next two weeks by monitoring the mice's weight, evaluating the left ventricle ejection fraction, and assessing the histology of the heart tissue at the end of the experiment. Higher cell density showed significantly greater efficiency in MI mice treatment in terms of weight gain and the recovery of ejection fraction. The heart tissue of the groups receiving cell sheets showed human-CD44-positive staining and reduced fibrosis and apoptosis. In conclusion, the hUC-MSC sheets ameliorated heart MI injury in mice and the efficacy of the cell sheets improved as the number of cells increased.