Pathogenesis Of Myocardial Infarction Research Articles

Spatiotemporal control of neutrophil fate to tune inflammation and repair for myocardial infarction therapy

Neutrophils are critical mediators of both the initiation and resolution of inflammation after myocardial infarction (MI). Overexuberant neutrophil signaling after MI exacerbates cardiomyocyte apoptosis and cardiac remodeling while neutrophil apoptosis at the injury site promotes macrophage polarization toward a pro-resolving phenotype. Here, we describe a nanoparticle that provides spatiotemporal control over neutrophil fate to both stymie MI pathogenesis and promote healing. Intravenous injection of roscovitine/catalase-loaded poly(lactic-co-glycolic acid) nanoparticles after MI leads to nanoparticle uptake by circulating neutrophils migrating to the infarcted heart. Activated neutrophils at the infarcted heart generate reactive oxygen species, triggering intracellular release of roscovitine, a cyclin-dependent kinase inhibitor, from the nanoparticles, thereby inducing neutrophil apoptosis. Timely apoptosis of activated neutrophils at the infarcted heart limits neutrophil-driven inflammation, promotes macrophage polarization toward a pro-resolving phenotype, and preserves heart function. Modulating neutrophil fate to tune both inflammatory and reparatory processes may be an effective strategy to treat MI.

The mechanism and treatment strategies of GSDMD-mediated pyroptosis in myocardial infarction

Acute myocardial infarction (MI) is associated with high morbidity and mortality and poses a significant challenge to human health. Despite advances in medicine, effective treatment options for MI are still associated with adverse outcomes, such as heart failure. Consequently, identifying the pathogenesis of MI is a promising avenue for developing practical treatments. The inflammatory response plays a critical role in the pathogenesis of MI. Gasdermin D (GSDMD)-mediated pyroptosis regulates the inflammatory response, which is a pathogenic and potential therapeutic target for MI. Therefore, anti-pyroptosis treatment is emerging as a promising therapeutic approach for MI. Overall, this article reviews the mechanism and treatment strategies for GSDMD-mediated pyroptosis in MI, with the hope of providing insights into pathogenic interventions.

The choice of a method for restoring coronary blood flow in myocardial infarction with ST segment elevation (literature review)

In the structure of total mortality, cardiovascular diseases are in the first place in the world. The main and most common reason for this is the incidence of myocardial infarction (MI). The basis of the pathogenesis of MI with ST elevation is persistent and complete thrombotic occlusion of the large epicardial branch of the coronary artery, leading to extensive necrosis of the heart muscle with the development of life-threatening complications, including death, the frequency of which is 8–10 %. The prognosis for MI is influenced by the presence of risk factors, complications, hemodynamic status, polymorbidity, as well as tactics for restoring coronary blood flow. To eliminate acute coronary artery occlusion, conservative treatment is used – thrombolytic therapy, surgical – primary percutaneous intervention, thromboextraction, coronary bypass surgery, as well as their combination. Today, there are scattered and isolated studies characterizing the approach to treatment in patients with MI with ST elevation in various diseases and with polymorbid pathology, the relationship with risk factors and laboratory and instrumental data has not been established, among which predictors of rapid response and death in patients with polymorbid pathology for emergency physicians have not been determined. It can be assumed that the chosen optimal patient management tactics in a specific clinical situation, taking into account the above-mentioned factors, will reduce the development of complications and increase the survival rate of patients with MI.

A Whole-Course-Repair System Based on Stimulus-Responsive Multifunctional Hydrogels for Myocardial Tissue Regeneration.

Myocardial infarction (MI) has emerged as the predominant cause of cardiovascular morbidity globally. The pathogenesis of MI unfolds as a progressive process encompassing three pivotal phases: inflammation, proliferation, and remodeling. Smart stimulus-responsive hydrogels have garnered considerable attention for their capacity to deliver therapeutic drugs precisely and controllably at the MI site. Here, a smart stimulus-responsive hydrogel with a dual-crosslinked network structure is designed, which enables the precise and controlled release of therapeutic drugs in different pathological stages for the treatment of MI. The hydrogel can rapidly release curcumin (Cur)in the inflammatory phase of MI to exert anti-apoptotic/anti-inflammatory effects. Recombinant humanized collagen type III (rhCol III) is loaded in the hydrogel and released as the hydrogel swelled/degraded during the proliferative phase to promote neovascularization. RepSox (a selective TGF-β inhibitor) releases from Pluronic F-127 grafted with aldehyde nanoparticles (PF127-CHO@RepSox NPs) in the remodeling phase to against fibrosis. The results in vitro and in vivo suggest that the hydrogel improves cardiac function and alleviates cardiac remodeling by suppressing inflammation and apoptosis, promoting neovascularization, and inhibiting myocardial fibrosis. A whole-course-repair system, leveraging stimulus-responsive multifunctional hydrogels, demonstrates notable effectiveness in enhancing post-MI cardiac function and facilitating the restoration of damaged myocardial tissue.

Pyroptosis and mitochondrial function participated in miR-654-3p-protected against myocardial infarction

Myocardial infarction (MI) is one of the leading causes of heart failure with highly complicated pathogeneses. miR-654-3p has been recognized as a pivotal regulator of controlling cell survival. However, the function of miR-654-3p in cardiomyocytes and MI has yet to be reported. This study aimed to identify the role of miR-654-3p in the regulation of myocardial infarction. To understand the contribution of miR-654-3p on heart function, we generated cardiac-specific knockdown and overexpression mice using AAV9 technology in MI injury. Mechanically, we combined cellular and molecular techniques, pharmaceutical treatment, RNA sequencing, and functional testing to elucidate the potential pathological mechanisms. We identified that mice subjected to MI decreased the expression of miR-654-3p in the border and infarcted area. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. Furthermore, we found a deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death but not other programmed cell death. Intriguingly, miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Cardiac elevating miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Using RNA sequence and molecular biological approaches, we found overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function. Our finding identified the character of miR-654-3p in protecting against MI damage by mediating pyroptosis and mitochondrial metabolism. These findings provide a new mechanism for miR-654-3p involvement in the pathogenesis of MI and reveal novel therapeutic targets.miR-654-3p expression was decreased after MI. Mice lacking miR-654-3p in the heart showed some inflammation infiltration and myocardial fibrosis, resulting in a mild cardiac injury. The deficiency of miR-654-3p in cardiomyocytes resulted in pyroptotic cell death. miR-654-3p deficiency aggravated MI-induced cardiac dysfunction, accompanied by higher myocardial fibrosis and cardiac enzymes and augmented pyroptosis activation. Overexpression of miR-654-3p prevented myocardial fibrosis and inflammation infiltration and decreased pyroptosis profile, thereby attenuating MI-induced cardiac damage. Overexpression of miR-654-3p in the heart promoted the metabolic ability of the cardiomyocytes by promoting mitochondrial metabolism and mitochondrial respiration function.

Targeting the PANoptosis signaling pathway for myocardial protection: therapeutic potential of Xian Ling Gu Bao capsule.

Introduction: Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms. Methods: This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting. Results: The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection. Conclusion: In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.

Annexin A1-Loaded Alginate Hydrogel Promotes Cardiac Repair via Modulation of Macrophage Phenotypes after Myocardial Infarction.

Myocardial infarction (MI) is associated with inflammatory reaction, which is a pivotal component in MI pathogenesis. Moreover, excessive inflammation post-MI can lead to cardiac dysfunction and adverse remodeling, emphasizing the critical need for an effective inflammation-regulating treatment for cardiac repair. Macrophage polarization is crucial in the inflammation process, indicating its potential as an adjunct therapy for MI. In this study, we developed an injectable alginate hydrogel loaded with annexin A1 (AnxA1, an endogenous anti-inflammatory and pro-resolving mediator) for MI treatment. In vitro results showed that the composite hydrogel had good biocompatibility and consistently released AnxA1 for several days. Additionally, this hydrogel led to a reduced number of pro-inflammatory macrophages and an increased proportion of pro-healing macrophages via the adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mammalian target of the rapamycin (mTOR) axis. Furthermore, the intramyocardial injection of this composite hydrogel into a mouse MI model effectively modulated macrophage transition to pro-healing phenotypes. This transition mitigated early inflammatory responses and cardiac fibrosis, promoted angiogenesis, and improved cardiac function. Therefore, our study findings suggest that combining biomaterials and endogenous proteins for MI treatment is a promising approach for limiting adverse cardiac remodeling, preventing cardiac damage, and preserving the function of infarcted hearts.

Biological Signaling Network in Myocardial Infarction in Young Adults. A Study of Transcriptome Analysis

Background: Myocardial infarction (MI) is the common manifestation of coronary heart disease that develops from occlusion of coronary arteries. Several risk factors of MI were identified, but data pertaining to genetics and molecular mechanisms involved in the development of MI is limited. Therefore, the present study attempts to analyze the peripheral blood transcriptome information of MI patients and unveil the key genes involved in the pathogenesis of MI. Methods: Total RNA was extracted from the blood sample for illumine sequencing, and raw data obtained were subjected to quality control (QC) using the FastQC tool, followed by trimming of raw data by the fastp tool. Further processed high-quality data were aligned onto the human reference genome using HISAT2 aligner. Gene quantification was done using the feature Counts plugin in the subread package. The raw read counts were given as input to the differential expression analysis (DESeq2) R package for the computation of differentially expressed genes. Gene set enrichment analysis for gene ontology was done using the clusterProfiler R package. Results: A total of 609 genes were significantly expressed in the present study, of which 561 genes were upregulated and 48 genes were downregulated. This study presents overall changes in genes involved in different categories such as biological processes, molecular functions, and cellular components in responses to MI. Conclusions: The significantly deregulated genes identified in the present study not only indicate the molecular and cellular changes but also suggest the scope for the detection of specific gene markers for MI.

Opposite causal effects of birthweight on myocardial infarction and atrial fibrillation and the distinct mediating pathways: a Mendelian randomization study

BackgroundPrevious observational studies have documented an inverse association of birthweight with myocardial infarction (MI) but a positive association with atrial fibrillation (AF). However, the causality of these associations and the underlying mediating pathways remain unclear. We aimed to investigate the causal effects of birthweight, incorporating both fetal and maternal genetic effects, on MI and AF, and identify potential mediators in their respective pathways.MethodsWe performed Mendelian randomization (MR) analyses using genome-wide association study summary statistics for birthweight (N = 297,356 for own birthweight and 210,248 for offspring birthweight), MI (Ncase=61,000, Ncontrol=577,000), AF (Ncase=60,620, Ncontrol=970,216), and 52 candidate mediators (N = 13,848-1,295,946). Two-step MR was employed to identify and assess the mediation proportion of potential mediators in the associations of birthweight with MI and AF, respectively. As a complement, we replicated analyses for fetal-specific birthweight and maternal-specific birthweight.ResultsGenetically determined each 1-SD lower birthweight was associated with a 40% (95% CI: 1.22–1.60) higher risk of MI, whereas each 1-SD higher birthweight was causally associated with a 29% (95% CI: 1.16–1.44) higher risk of AF. Cardiometabolic factors, including lipids and lipoproteins, glucose and insulin, blood pressure, and fatty acids, each mediated 4.09-23.71% of the total effect of birthweight on MI, followed by body composition and strength traits (i.e., appendicular lean mass, height, and grip strength) and socioeconomic indicators (i.e., education and household income), with the mediation proportion for each factor ranging from 8.08 to 16.80%. By contrast, appendicular lean mass, height, waist circumference, childhood obesity, and body mass index each mediated 15.03-45.12% of the total effect of birthweight on AF. Both fetal-specific birthweight and maternal-specific birthweight were inversely associated with MI, while only fetal-specific birthweight was positively associated with AF. Psychological well-being and lifestyle factors conferred no mediating effect in either association.ConclusionsCardiometabolic factors mainly mediated the association between lower birthweight and MI, while body composition and strength traits mediated the association between higher birthweight and AF. These findings provide novel evidence for the distinct pathogenesis of MI and AF and advocate adopting a life-course approach to improving fetal development and subsequent causal mediators to mitigate the prevalence and burden of cardiovascular diseases.

Differential expression and implication of m6A methylation in mice with experimental myocardial infarction

Objective: To define differentially expressed N6-adenylate methylation (m6A) genes in the myocardial tissue of mice with myocardial infarction (MI) and explore its potential impact on the pathological process of MI. Methods: The random number table method was used to divide the eighteen SPF C57BL/6J male mice aged from 8 to 10 weeks into MI group (MI group, n=9) and control group (control group, n=9). Modified m6A genes from the myocardial tissue were detected via methylated RNA immunoprecipitation with the next generation sequencing (MeRIP-seq). We explored methylation modified characteristics, verified mRNA expression and m6A modified level by bioinformatics analysis, qPCR and MeRIP-qPCR. Results: The Heatmap revealed that 901 differentially modified m6A genes between MI and control group, of which 537 genes were upregulated, and 364 genes were downregulated. The principal component analysis affirmed that two groups could be distinguished significantly in terms of m6A gene modification. The characteristic sequence of m6A modification was GGACU and mainly concentrated in the coding sequence. According to the conjoint analysis with RNA-seq and MeRIP-seq, 119 genes expressed simultaneous m6A modification difference and mRNA expression difference. The Venn diagram exhibited the positive and negative correlation between m6A modification and mRNA expression. Besides, the GO enrichment analysis indicated that the genes with m6A differential modification in MI group were mainly involved in heart development and other processes. qPCR verified that Gbp6 was up-regulated, while Dnaja1 and Dnajb1 were down-regulated. MeRIP-qPCR revealed that the m6A modification level of Hspa1b was downregulated. Conclusion: Myocardial infarction induces differential modification of m6A in the mice model. In addition, the genes with m6A modification may be affected by methylation related enzymes, thus participating the pathogenesis of MI by regulating apoptosis and inflammation.

Exploring Shared Biomarkers of Myocardial Infarction and Alzheimer's Disease via Single-Cell/Nucleus Sequencing and Bioinformatics Analysis.

Patients are at increased risk of dementia, including Alzheimer's disease (AD), after myocardial infarction (MI), but the biological link between MI and AD is unclear. To understand the association between the pathogenesis of MI and AD and identify common biomarkers of both diseases. Using public databases, we identified common biomarkers of MI and AD. Least absolute shrinkage and selection operator (LASSO) regression and protein-protein interaction (PPI) network were performed to further screen hub biomarkers. Functional enrichment analyses were performed on the hub biomarkers. Single-cell/nucleus analysis was utilized to further analyze the hub biomarkers at the cellular level in carotid atherosclerosis and AD datasets. Motif enrichment analysis was used to screen key transcription factors. 26 common differentially expressed genes were screened between MI and AD. Function enrichment analyses showed that these differentially expressed genes were mainly associated with inflammatory pathways. A key gene, Regulator of G-protein Signaling 1 (RGS1), was obtained by LASSO regression and PPI network. RGS1 was confirmed to mainly express in macrophages and microglia according to single-cell/nucleus analysis. The difference in expression of RGS1 in macrophages and microglia between disease groups and controls was statistically significant (p < 0.0001). The expression of RGS1 in the disease groups was upregulated with the differentiation of macrophages and microglia. RelA was a key transcription factor regulating RGS1. Macrophages and microglia are involved in the inflammatory response of MI and AD. RGS1 may be a key biomarker in this process.

Analysis of C-reactive protein and lactoferrin levels in patients with myocardial infarction with chronic obstructive pulmonary disease depending on presence of complications

Purpose. To analyze the levels of C-reactive protein (CRP) and lactoferrin (LF) in patients with myocardial infarction (MI) with chronic obstructive pulmonary disease (COPD) depending on the presence of acute MI complications.Materials and methods. In total were examined 325 patients with MI: 195 patients with acute MI + COPD and 130 MI patients without COPD and 110 healthy somatic subjects. Complications of acute MI were observed in 84 (43.1 %) MI + COPD patients and in 32 (24.6 %) MI patients without COPD.Results of the study. The level of inflammatory markers we studied was elevated in all observation groups relative to controls. In MI + COPD patients and in MI patients without COPD the level of highly sensitive CRP was statistically significantly higher in the presence of acute period complications. LF levels did not depend on the presence of complications in any of the observation groups.Conclusions. Increased inflammatory markers in MI patients without COPD and in MI + COPD groups indicate the significance of the inflammatory component in the pathogenesis of MI. In patients with MI + COPD the severity of systemic inflammation is maximal. CRP is informative as an indicator of inflammatory response in MI. The highest CRP level was observed in patients with complicated MI.

MiR-206 may regulate mitochondrial ROS contribute to the progression of Myocardial infarction via TREM1

Myocardial infarction (MI) is a leading cause of mortality. To better understand its molecular and cellular mechanisms, we used bioinformatic tools and molecular experiments to explore the pathogenesis and prognostic markers. Differential gene expression analysis was conducted using GSE60993 and GSE66360 datasets. Hub genes were identified through pathway enrichment analysis and PPI network construction, and four hub genes (AQP9, MMP9, FPR1, and TREM1) were evaluated for their predictive performance using AUC and qRT-PCR. miR-206 was identified as a potential regulator of TREM1. Finally, miR-206 was found to induce EC senescence and ER stress through upregulating mitochondrial ROS levels via TREM1. These findings may contribute to understanding the pathogenesis of MI and identifying potential prognostic markers.

Animal Models and Methods of Myocardial Infarction Induction and the Role of Tissue Engineering in the Regeneration of Damaged Myocardium.

The introduction of an experimental animal model for myocardial infarction (MI) has particular importance. Research done on large animals provides valuable information for the researchers because of the similar characteristics of their hearts compared to humans, but the cost of purchasing and maintaining them is high. In comparison, using small animals has advantages, such as they are easy to work with and have low purchase and maintenance costs. However, in some of these animals, due to less similarity of the heart to humans, they cannot simulate the natural pathogenesis of human MI. Moreover, there are different methods for the induction of MI in animals; each has its own advantages and disadvantages. However, a method must be chosen to simulate the natural pathogenesis of MI with minimal complication. Currently, attempts are being made for myocardial regeneration after MI using the direct transplantation of stem cells or an engineered scaffold. The scaffold creates a 3D ambiance for the cultured cells. The task of tissue engineering is to optimize the scaffold with appropriate systems for the separation, proliferation, and differentiation of the desired cells until they are capable of promoting the threedimensional and appropriate growth of the tissue. The purpose of tissue engineering in cardiac is the use of scaffolds and cells in the damaged area, followed by the improvement of the heart function through automatic pulsation, communication with the host vessels, and electrical coupling with the myocardium, eventually creating a force to increase the heart function.

Lymphatic insufficiency leads to distinct myocardial infarct content assessed by magnetic resonance TRAFFn, T1ρ and T2 relaxation times

The role of cardiac lymphatics in the pathogenesis of myocardial infarction (MI) is unclear. Lymphatic system regulates cardiac physiological processes such as edema and tissue fluid balance, which affect MI pathogenesis. Recently, MI and fibrosis have been assessed using endogenous contrast in magnetic resonance imaging (MRI) based on the relaxation along a fictitious field with rank n (RAFFn). We extended the RAFFn applications to evaluate the effects of lymphatic insufficiency on MI with comparison to longitudinal rotating frame (T1ρ) and T2 relaxation times. MI was induced in transgenic (TG) mice expressing soluble decoy VEGF receptor 3 that reduces lymphatic vessel formation and their wild-type (WT) control littermates for comparison. The RAFFn relaxation times with rank 2 (TRAFF2), and rank 4 (TRAFF4), T1ρ and T2 were acquired at time points 0, 3, 7, 21 and 42 days after the MI at 9.4 T. Infarct sizes were determined based on TRAFF2, TRAFF4, T1ρ and T2 relaxation time maps. The area of differences (AOD) was calculated based on the MI areas determined on T2 and TRAFF2, TRAFF4 or T1ρ relaxation time maps. Hematoxylin–eosin and Sirius red stained histology sections were prepared to confirm MI locations and sizes. MI was detected as increased TRAFF2, TRAFF4, T1ρ and T2 relaxation times. Infarct sizes were similar on all relaxation time maps during the experimental period. Significantly larger AOD values were found together with increased AOD values in the TG group compared to the WT group. Histology confirmed these findings. The lymphatic deficiency was found to increase cardiac edema in MI. The combination of TRAFF2 (or TRAFF4) and T2 characterizes MI and edema in the myocardium in both lymphatic insufficiency and normal mice without any contrast agents.

SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity

Small ubiquitin-related modifier (SUMOylation) is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload. However, the function of SUMOylation after myocardial infarction (MI) and the molecular details of heart cell responses to SUMO1 deficiency have not been determined. In this study, we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI. However, SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury. Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells. Among cardiomyocytes, SUMO1 deletion increased the Nppa+Nppb+Ankrd1+ cardiomyocyte subcluster proportion after MI. In addition, the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice. Importantly, SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes. Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium. Mice preinjected with cardiomyocyte-specific AAV-SUMO1, but not the endothelial cell-specific form, and exhibited ameliorated cardiac remodeling following MI. Collectively, our results identified the role of SUMO1 in cardiomyocytes, fibroblasts, and endothelial cells after MI. These findings provide new insights into SUMO1 involvement in the pathogenesis of MI and reveal novel therapeutic targets.

Modulation of the miR-122/Sirt-6/ACE2 axis on experimentally-induced myocardial infarction

Myocardial infarction (MI) is a progressive myocardial necrosis that can lead to a number of life-threatening complications. MiRNAs have a crucial role in the pathogenesis of many cardiovascular diseases. Remarkably, miR-122 targets the sirtuin-6 (Sirt-6) gene, which is an essential regulator of cardiovascular function and is considered a partial angiotensin converting enzyme 2 (ACE2) activator. Modulation of this axis is supposed to contribute to MI pathogenesis. The current study aims to investigate the cardioprotective effects of xanthenone through targeting the miR-122/Sirt-6/ACE2 axis on experimentally-induced MI in rats. Xanthenone was administered for 14 days and isoprenaline was injected in the last 2 days of the experiment. Xanthenone treatment resulted in a significant downregulation of miR-122, which further upregulated Sirt-6 and thus activated the adenosine monophosphate-activated protein kinase (AMPK). AMPK increases ACE2 levels and results in a decrease in the level of its substrate angiotensin II resulting in the normalization of the inflammatory cytokines and the cardiac biomarkers. Finally, by targeting the miR-122/Sirt-6/AMPK/ACE2 axis, xanthenone has the potential to be a promising cardioprotective agent against MI.

The Role of the Notch Signaling Pathway in Recovery of Cardiac Function after Myocardial Infarction.

Myocardial infarction (MI) is a pathological process, evidencing as massive death of cardiomyocytes associated with hypoxic and oxidative stress. The formation of areas of fibrosis ultimately leads to heart failure. There are some mechanisms that contribute to the functional repair of the heart. In most mammals, including humans, the Notch signaling pathway has cardioprotective effects. It is involved in the formation of the heart in embryogenesis and in the restoration of cardiac function after MI due to: (1) reducing oxidative stress; (2) prevention of apoptosis; (3) regulation of inflammation; (4) containment of fibrosis and hypertrophy of cardiomyocytes; (5) tissue revascularization; and (6) regulation of proliferation and differentiation of cardiomyocytes. In addition, the Notch signaling pathway interacts with other signaling cascades involved in the pathogenesis of MI and subsequent cardiac repair. In this review, we consider the Notch signaling pathway as a potential target for therapeutic approaches aimed at improving cardiac recovery after MI.

The circRNA-miRNA/RBP regulatory network in myocardial infarction.

Myocardial infarction (MI) is a serious heart disease that causes high mortality rate worldwide. Noncoding RNAs are widely involved in the pathogenesis of MI. Circular RNAs (circRNAs) are recently validated to be crucial modulators of MI. CircRNAs are circularized RNAs with covalently closed loops, which make them stable under various conditions. CircRNAs can function by different mechanisms, such as serving as sponges of microRNAs (miRNAs) and RNA-binding proteins (RBPs), regulating mRNA transcription, and encoding peptides. Among these mechanisms, sponging miRNAs/RBPs is the main pathway. In this paper, we systematically review the current knowledge on the properties and action modes of circRNAs, elaborate on the roles of the circRNA-miRNA/RBP network in MI, and explore the value of circRNAs in MI diagnosis and clinical therapies. CircRNAs are widely involved in MI. CircRNAs have many advantages, such as stability, specificity, and wide distribution, which imply that circRNAs have a great potential to act as biomarkers for MI diagnosis and prognosis.

Valencene post-treatment exhibits cardioprotection via inhibiting cardiac hypertrophy, oxidative stress, nuclear factor- κB inflammatory pathway, and myocardial infarct size in isoproterenol-induced myocardial infarcted rats; A molecular study

The growing burden of myocardial infarction (MI) becomes a major global health issue that is accountable for considerable mortality worldwide. Hence, it is obligatory to develop a new treatment for MI having lesser side effects. Cardiac hypertrophy, oxidative stress, and inflammatory pathways play crucial roles in the pathogenesis of MI. This investigation established the anti-cardiac hypertrophic, antioxidant, anti-inflammatory, and myocardial infarct size limiting effects of valencene. Rats were induced MI by isoproterenol (100 mg/kg body weight) and then treated with valencene and cardiac sensitive markers, cardiac hypertrophy, oxidative stress, markers of inflammation, nuclear factor- κB inflammatory pathway, and myocardial infarct size was estimated/determined. The serum cardiac diagnostic markers, cardiac hypertrophy, conjugated dienes, markers of inflammation, pro-inflammatory cytokines, and myocardial infarct size were significantly (P < 0.05) increased by isoproterenol. Further, antioxidant enzymes and anti-inflammatory cytokine gene were significantly (P < 0.05) decreased in the heart. The 2, 3, 5-triphenyl tetrazolium chloride dye staining revealed a larger infarct size. Moreover, histological results of myocardial infarcted rat's cardiac tissue revealed separation of cardiac muscle fibers, necrosis, and inflammatory cells. Post-treatment with valencene (12 mg/kg body weight) orally, daily, for two weeks to isoproterenol-induced myocardial infarcted rats reversed all above said structural, biochemical, molecular, and histological parameters investigated, by its anti-cardiac hypertrophic, antioxidant, anti-inflammatory, and myocardial infarct size limiting effects. Thus, valencene is a potential candidate for inhibiting cardiac hypertrophy, oxidative stress, nuclear factor- κB inflammatory pathway, and myocardial infarct size and exhibited cardioprotection in MI.