Abstract Acute Myocardial Infarction Research Articles

Growth factors: avenues for the treatment of myocardial infarction and potential delivery strategies.

Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Despite recent advances in clinical management, reoccurence of heart failure after AMI remains high, in partbecause of the limited capacity of cardiac tissue to repairafter AMI-induced cell death. Growth factor-based therapy has emerged as an alternative AMI treatment strategy. Understanding the underlying mechanisms of growth factor cardioprotective and regenerative actions is important. This review focuses on the function of different growth factors at each stage of the cardiac repair process. Recent evidence for growth factor therapy in preclinical and clinical trials is included. Finally, different delivery strategies are reviewed with a view to providing workable strategies for clinical translation.

Extracellular Vesicle-Derived circITGB1 Regulates Dendritic Cell Maturation and Cardiac Inflammation via miR-342-3p/NFAM1.

Acute myocardial infarction (AMI) is a complication of atherosclerosis-related cardiovascular illness that is caused by prolonged ischemia. Circular RNAs (circRNAs) are concentrated in extracellular vesicles (EVs) and have been linked to cardiovascular disease. However, additional research is needed into the expression and function of circRNAs in AMI. In this study, circITGB1 (has_circRNA_0018146), derived from exon 1 of the ITGB1 gene localized on chromosome 10, was shown to be considerably increased in plasma from patients with AMI compared to healthy controls, as demonstrated by the comparison of EV-circRNA expression patterns. Using a luciferase screening assay and a biotin-labeled circITGB1 probe to identify microRNA(s) complementary to circITGB1 sequences, we discovered that circITGB1 competitively binds to miR-342-3p and inhibits its expression, which in turn increase the expression of NFAT activating molecule 1 (NFAM1). Based on western blotting and immunological studies, circITGB1 controls dendritic cell maturation by targeting miR-342-3p and NFAM1. circITGB1 also exacerbated cardiac damage and regulated miR-342-3p and NFAM1 expression in a mouse AMI model. This implies that EV-circITGB1 is involved in dendritic cell maturation and cardiac damage via miR-342-3p/NFAM1, and that is linked to AMI-associated pathogenic processes.

Systematic Bioinformatics Analysis Based on Public and Second-Generation Sequencing Transcriptome Data: A Study on the Diagnostic Value and Potential Mechanisms of Immune-Related Genes in Acute Myocardial Infarction

Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases worldwide. Advances in genomics have provided new ideas for the development of novel molecular biomarkers of potential clinical value for AMI.MethodsBased on microarray data from a public database, differential analysis and functional enrichment analysis were performed to identify aberrantly expressed genes in AMI and their potential functions. CIBERSORT was used for immune landscape analysis. We also obtained whole blood samples of 3 patients with AMI and performed second-generation sequencing (SGS) analysis. Weighted gene co-expression network analysis (WGCNA) and cross-tabulation analysis identified AMI-related key genes. Receiver operating characteristic (ROC) curves were used to assess the diagnostic power of key genes. Single-gene gene set enrichment analysis (GSEA) revealed the molecular mechanisms of diagnostic indicators.ResultsA total of 53 AMI-related DEGs from a public database were obtained and found to be involved in immune cell activation, immune response regulation, and cardiac developmental processes. CIBERSORT confirmed that the immune microenvironment was altered between AMI and normal samples. A total of 77 hub genes were identified by WGCNA, and 754 DEGs were obtained from own SGS data. Seven diagnostic indicators of AMI were obtained, namely GZMA, NKG7, TBX21, TGFBR3, SMAD7, KLRC4, and KLRD1. The single-gene GSEA suggested that the diagnostic indicators seemed to be closely implicated in cell cycle, immune response, cardiac developmental, and functional regulatory processes.ConclusionThe present study provides new diagnostic indicators for AMI and further confirms the feasibility of the results of genome-wide gene expression analysis.

N-glycan profiles of acute myocardial infarction patients reveal potential biomarkers for diagnosis, severity assessment and treatment monitoring.

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. Diagnostic challenges remain in this highly time-sensitive condition. Using capillary electrophoresis-laser-induced fluorescence, we analyzed the blood plasma N-glycan profile in a cohort study comprising 103 patients with AMI and 69 controls. Subsequently, the data generated was subjected to classification modeling to identify potential AMI biomarkers. An area under the Receiving Operating Characteristic curve (AUCROC) of 0.81 was obtained when discriminating AMI vs. non-MI patients. We postulate that the glycan profile involves a switch from a pro- to an anti-inflammatory state in the AMI pathophysiology. This was supported by significantly decreased levels in galactosylation, alongside increased levels in sialylation, afucosylation and GlcNAc bisection levels in the blood plasma of AMI patients. By substantiating the glycomics analysis with immunoglobulin G (IgG) protein measurements, robustness of the glycan-based classifiers was demonstrated. Changes in AMI-related IgG activities were also confirmed to be associated with alterations at the glycosylation level. Additionally, a glycan-biomarker panel derived from glycan features and current clinical biomarkers performed remarkably (AUCROC=0.90, sensitivity=0.579 at 5% false positive rate) when discriminating between patients with ST-segment elevation MI (n=84) and non-ST-segment elevation MI (n=19). Moreover, by applying the model trained using glycomics information, AMI and controls can still be discriminated at 1 and 6months after baseline. Thus, glycomics biomarkers could potentially serve as a valuable complementary test to current diagnostic biomarkers. Additional research on their utility and associated biomechanisms via a large-scale study is recommended.

Screening and bioinformatics analysis of key biomarkers in acute myocardial infarction

Abstract Acute myocardial infarction (AMI) is the most severe manifestation of coronary artery disease. Considerable efforts have been made to elucidate its etiology and pathology, but the genetic factors that play a decisive role in the occurrence of AMI are still unclear. To determine the molecular mechanism of the occurrence and development of AMI, four microarray datasets, namely, GSE29111, GSE48060, GSE66360, and GSE97320, were downloaded from the Gene Expression Omnibus (GEO) database. We analyzed the four GEO datasets to obtain the differential expression genes (DEGs) of patients with AMI and patients with non-AMI and then performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Protein-protein interaction (PPI) network analysis. A total of 41 DEGs were identified, including 39 upregulated genes and 2 downregulated genes. The enriched functions and pathways of the DEGs included the inflammatory response, neutrophil chemotaxis, immune response, extracellular space, positive regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor activity, response to lipopolysaccharide, receptor for advanced glycation end products (RAGE) receptor binding, innate immune response, defense response to bacterium, and receptor activity. The cytoHubba plug-in in Cytoscape was used to select the most significant hub gene from the PPI network. Ten hub genes were identified, and GO enrichment analysis revealed that these genes were mainly enriched in inflammatory response, neutrophil chemotaxis, immune response, RAGE receptor binding, and extracellular region. In conclusion, this study integrated four datasets and used bioinformatics methods to analyze the gene chips of AMI samples and control samples and identified DEGs that may be involved in the occurrence and development of AMI. The study provides reliable molecular biomarkers for AMI screening, diagnosis, and prognosis.

Incidence and Outcomes of Registry-Based Acute Myocardial Infarction After Aneurysmal Subarachnoid Hemorrhage.

Acute myocardial infarction (AMI) is the rarest and least studied cardiac complication of aneurysmal subarachnoid hemorrhage (aSAH). Precise estimates of the incidence of AMI after aSAH are unavailable. Our goal was to estimate the incidence of registry-based AMI (rb-AMI) after aSAH and determine its association with clinical outcomes. Adult patients with aSAH in the National Inpatient Samples from 2002 to 2014 were included in the study. We evaluated risk factors for rb-AMI using univariate and multivariate regression models. Clinical outcomes that were assessed included functional status at discharge, in-patient mortality, length of stay, and total hospitalization cost, adjusting for patient demographics and cardiovascular risk factors through an inverse probability weighted analysis. Subgroup analyses were further performed stratified by rb-AMI type (ST-segment elevation myocardial infarction [STEMI] vs. non-STEMI [NSTEMI]). A total of 139,734 patients with aSAH were identified, 3.6% of whom had rb-AMI. NSTEMI was the most common type of rb-AMI occurring after aSAH (71% vs. 29% for NSTEMI vs. STEMI, respectively). Patient characteristics associated with higher odds of rb-AMI included age, female sex, poor aSAH grade, and various cardiovascular risk factors. Rb-AMI was also associated with poor functional status at discharge, higher in-hospital mortality, and a longer and more costly hospital stay. Rb-AMI occurs in 3.6% of patients with aSAH and is associated with poor functional status at discharge, higher in-patient mortality, and a longer and more costly hospitalization. Differentiating between different types of rb-AMI would be important in optimizing the management of patients with aSAH. Our definition of rb-AMI likely includes patients with neurogenic stress cardiomyopathy, which may confound the results.

Trelagliptin ameliorates oxygen-glucose deprivation/reperfusion (OGD/R)-induced mitochondrial dysfunction and metabolic disturbance of endothelial cells.

Acute myocardial infarction (AMI) is a severe cardiovascular disease with high mortality. It is reported to be closely related to the mitochondrial dysfunction and metabolic disturbance on endothelial cells under a chronic hypoxic state. Significant declined mitochondrial respiration, ATP production, and metabolic changes are the main characteristics of endothelial injury in the disease. Trelagliptin is a DPP-4 inhibitor applied for the treatment of type II diabetes and has been recently reported to exert various pharmacological properties. In this investigation, we examined whether Trelagliptin possessed a protective effect against mitochondrial dysfunction and metabolic disturbance in human aortic valvular endothelial cells (HAVECs) under oxygen-glucose deprivation/reperfusion (OGD/R) conditions. We found that both the cytotoxicity and mitochondrial oxidative stress in HAVECs induced by OGD/R stimulation were greatly alleviated by Trelagliptin. In addition, the declined mitochondrial respiration and ATP production decreased secretion of cystathionine and creatine, and the increased production of triglyceride and adiponectin in OGD/R-challenged HAVECs was dramatically reversed by Trelagliptin, accompanied by the upregulated expression level of PGC-1α and CPT-1. Lastly, the AMPK pathway was observed to be significantly activated in OGD/R-challenged HAVECs by Trelagliptin treatment. After co-administration of the inhibitor of the AMPK pathway, the effects of Trelagliptin on mitochondrial function and metabolic alterations were significantly abolished. Taken together, our data indicate that Trelagliptin ameliorated OGD/R-induced mitochondrial disturbance and metabolic changes by activating the AMPK pathway.

Association between winter cold spells and acute myocardial infarction in Lithuania 2000\u20132015

Acute myocardial infarction (AMI) is a major public health problem. Cold winter weather increases the risk of AMI, but factors influencing susceptibility are poorly known. We conducted an individual-level case-crossover study of the associations between winter cold spells and the risk of AMI, with special focus on survival at 28 days and effect modification by age and sex. All 16,071 adult cases of AMI among the residents of the city of Kaunas in Lithuania in 2000–2015 were included in the study. Cold weather was statistically defined using the 5th percentile of frequency distribution of daily mean temperatures over the winter months. According to conditional logistic regression controlling for time-varying and time-invariant confounders, each additional cold spell day during the week preceding AMI increased the risk of AMI by 5% (95% CI 1–9%). For nonfatal and fatal cases, the risk increase per each additional cold spell day was 5% (95% CI 1–9%) and 6% (95% CI − 2–13%), respectively. The effect estimate was greater for men (OR 1.07, 95% CI 1.02–1.12) than for women (OR 1.02, 95% CI 0.97–1.08), but there was no evidence of effect modification by age. Evidence on factors increasing susceptibility is critical for targeted cold weather planning.

Acute Myocardial Infarction of the Left Main Coronary Artery Presenting with Cardiogenic Shock and Pulmonary Edema during Noncardiac Surgery

Acute myocardial infarction (AMI) caused by severe stenosis of left main coronary artery (LMCA) presenting with cardiogenic shock and pulmonary edema during noncardiac surgery is uncommon, but a catastrophic event. A 77-year-old male with cholangiocarcinoma underwent hepatectomy. During the surgery, he presented with cardiogenic shock, which did not respond to infusion administration or vasopressor. A transesophageal echocardiogram revealed anterior, septal, and lateral severe hypokinesia and impaired left ventricular function. Emergent coronary angiogram showed severe stenosis of LMCA. The patient underwent primary percutaneous coronary intervention (PCI) under the support of intra-aortic balloon pump, followed by extracorporeal membrane oxygenation. The chest roentgenogram showed pulmonary edema. Two days after PCI, he successfully underwent hepatectomy and bile duct resection. Early identification of the cause of hemodynamic instability during noncardiac surgery and invasive strategy are important for minimizing the myocardial injury and improving clinical outcomes in AMI of LMCA.

Pharmacological Treatment of Tachyarrhythmias in Acute Myocardial Infarction - a Review

Abstract Acute myocardial infarction (AMI) causes severe metabolic and electrophysiological changes that induce silent or symptomatic life-threatening arrhythmias. Ventricular arrhythmias and atrial fibrillation are common during the early phase of AMI and are also important prognostic factors. Rapid identification and treatment of these arrhythmias can be life-saving, since in-hospital mortality rises dramatically in patients who develop arrhythmias with a fast ventricular rate following an AMI. Along with myocardial revascularization, adequate pharmacological therapy of hemodynamically relevant arrhythmias is generally useful. Since there are no controlled randomized trials comparing different antiarrhythmic drugs (AADs) in AMI, optimal decision making is based on medical societies guidelines recommendations and clinical judgement.

Inhibition of microRNA-495 inhibits hypoxia-induced apoptosis in H9c2 cells via targeting NFIB.

Acute myocardial infarction (AMI) is a serious cardiovascular disease that threatens human life. MicroRNA is considered to be an important participant in the pathophysiology of AMI. This article focused on the role of microRNA-495 (miR-495) in regulating apoptosis after myocardial infarction (MI) and its underlying mechanisms. H9c2 cells were cultured in an incubator containing 1% O2 to establish a cell model of MI. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was utilized to detect miR-495 expression in H9c2 cells. The effects of miR-495 and NFIB on hypoxia-treated H9c2 cells were observed by Western blot, lactate dehydrogenase (LDH) detection, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, flow cytometry, and terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) staining. Luciferase reporter gene experiment was used to prove the regulatory relationship between miR-495 and NFIB. Hypoxia induced injury to H9c2 cells, which was manifested by decreased cell viability, increased LDH release, increased pro-apoptotic proteins (Bax, Cleaved Caspase-3) expression, decreased anti-apoptotic protein (Bcl-2) expression, and increased in the rate of apoptosis and TUNEL positive cells. MiR-495 expression was remarkably increased in H9c2 cells treated with hypoxia. Inhibiting miR-495 expression markedly alleviated the hypoxia-induced injury in H9c2 cells, while silencing NFIB aggravated the hypoxia-induced damage. In addition, NFIB was confirmed to be the target of miR-495. MiR-495 expression was increased in hypoxia-treated H9c2 cells. Silencing miR-495 could significantly inhibit hypoxia-induced apoptosis of H9c2 cells by targeting NFIB.

Upregulation of miR-335 reduces myocardial injury following myocardial infarction via targeting MAP3K2.

Acute myocardial infarction (AMI) is a serious cardiovascular disease with a high incidence worldwide and the main cause of sudden cardiac death. The aim of this article was to study the protective role of miR-335 in myocardial infarction (MI) and the underlying molecular mechanism. Thirty Sprague Dawley (SD) rats were randomly divided into sham group, MI + NC group and MI + agomiR-335 group. The expression of miR-335 in rat myocardium was detected by quantitative Real Time-Polymerase Chain Reaction (RT-PCR). Western blot was performed to detect the expression of TNF-α, IL-6, IL-1β, Caspase-3, Cleaved Caspase-3 (C-Caspase-3) and MAP3K2 in rat myocardium. On the 7th day of the establishment of the rat MI model, a high-resolution small animal ultrasound system was utilized to detect the cardiac function of the rats, and the heart tissues and blood samples of the rats were collected. The corresponding kits were purchased to detect the contents of LDH, CK-MB, MDA and SOD in rat serum, and HE staining was employed to observe the morphology of rat myocardial tissue. The expression of miR-335 in myocardial infarcted zones and border zones of MI rats decreased significantly. The upregulation of miR-335 remarkably inhibited myocardial inflammation and apoptosis after MI, thus improving the cardiac function of MI rats. Compared with the sham group, the MAP3K2 expression in the MI + NC group was observably increased, while the overexpression of miR-335 could inhibit the expression of this protein. Through the Luciferase reporter gene experiment, we found that miR-335 could directly target MAP3K2. The expression of miR-335 decreased in myocardial tissue after MI, and the overexpression of miR-335 reduced myocardial damage by inhibiting oxidative stress, inflammation, and apoptosis via targeting MAP3K2, thereby improving the cardiac function of MI rats.

Inhibition of microRNA-346 inhibits myocardial inflammation and apoptosis after myocardial infarction via targeting NFIB.

Acute myocardial infarction (AMI) is a sudden cardiovascular event that endangers human life. MicroRNA is considered to be an important participant in the pathophysiology of myocardial infarction (MI). This article aim was to study the function and mechanisms of microRNA-346 (miR-346) on myocardium after MI. To study the role of miR-346 in MI, we established H2O2-induced H9c2 cell injury model and rat MI model. Real-time polymerase chain reaction (RT-PCR) was used to detect miR-346 expression. Western blot was utilized to measure the expression of Bcl-2, Bax, TNF-α, IL-6 and NFIB. Apoptosis of H9c2 cells was detected by TUNEL staining and flow cytometry. Enzyme-linked immunosorbent assay (ELISA) assay was utilized to measure the levels of TNF-α and IL-6 in supernatant. Assessment of left ventricular function in rats was performed using echocardiography. MiR-346 was significantly upregulated in H2O2-treated H9c2 cells and ischemic myocardium. In the H9c2 cell injury model, the expressions of Bax, TNF-α, and IL-6 were greatly increased while Bcl-2 expression was decreased, and the number of TUNEL-positive cells and apoptosis rate were also significantly increased. At the same time, the levels of TNF-α and IL-6 in the cell supernatant were markedly increased. However, after miR-346 expression was suppressed, these results were reversed. The expression of Bcl-2 increased, while the expression of Bax, TNF-α, and IL-6 decreased. The contents of TNF-α and IL-6 in the cell supernatant also decreased significantly. Both the number of TUNEL-positive cells and the apoptosis rate were markedly reduced. After injecting antagomir-346 into the myocardium of rats to silence miR-346, the cardiac function of MI rats was remarkably improved, and the LDH content in the serum of rats also decreased significantly. Using computational predictions tools, Western blotting and Luciferase activity assay, we found that nuclear factor I/B (NFIB) was targeted by miR-346. The expression of miR-346 was increased in H9c2 cells and ischemic myocardium of MI rats. Silencing miR-346 can significantly inhibit the inflammatory response and the apoptosis of cardiomyocytes by targeting NFIB.

Assessing Acute St-Elevation Myocardial Infarction With Prognostic Significance Of The Hyponatramia

Acute Myocardial Infarction (AMI) has become a significant public health issue in developed and developing nations, following extensive diagnostic and management research over recent decades. The study intended to research the prognostic values of inexplicable Hyponatremia in patients with severe STelevation of myocardial infarction, in 100 consecutive patients admitted to Tertiary care hospital. In the analysis, identified patients on admission were diagnosed with or produced Hyponatremia within 72 hours—a lower ejection fraction than those with usual amounts of sodium. The research aimed to evaluate the prognosis significance of Hyponatremia for the estimation of early death in acute ST-elevated myocardial infarction. One hundred straight patients admitted in the Coronary Centre Tertiary Care Facility with severe STelevated myocardial infarction were studied. The data of the study on various risk factors in association with the development of Hyponatremia like as age, sex, use of tobacco, diabetes, hypertension, ejection fraction etc. were analyzed. Thus, the researchers reported that in patients diagnosed with severe ST section escalation, Hyponatremia showed the initial emergence of hyponatremia myocardial infarctions. This condition correlates with the severity of LV dysfunction (in term of LVEF) and can be considered as an individual early death indicator as well as a prediction exacerbates with hyponatremia frequency.

NATIONAL TRENDS OF TOBACCO, ALCOHOL, AND DRUG ABUSE IN PATIENTS ADMITTED WITH ACUTE MYOCARDIAL INFARCTION

Acute myocardial infarction (AMI) is a huge health and economic burden in the US. Tobacco, alcohol and drug abuse (DA) are established risk factors. We sought to evaluate the national trend of use of each substance in patients admitted with AMI. We used the National Inpatient Sample between 2005

Significance of Extra-Hepatic Metabolism of Xenobiotics

Acute myocardial infarction (AMI) is the first manifestation of coronary heart disease, which is a critical threat to cause disability and death of human being5

The Mechanism Study of Dracocephalum Moldavica L. Total Flavonoids on Apoptosis induced by Myocardial Ischemia/Reperfusion injury in vivo and in vitro

Acute myocardial infarction (AMI) is the first manifestation of coronary heart disease, which is a critical threat to cause disability and death of human being5

A Simple Electrocardiographic Reading for Identifying the Culprit Site of Coronary Artery Occlusion in Inferior Wall Acute Myocardial Infarction

Acute myocardial infarction (AMI) usually occurs suddenly and is associated with a considerably high mortality rate.

Cardioprotection and effects of melatonin administration on cardiac ischemia reperfusion: Insight from clinical studies.

Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality. Many treatments have been identified that confer robust cardioprotection in experimental animal models of acute ischemia and reperfusion injury. However, translation of these cardioprotective therapies into the clinical setting of AMI for patient benefit has been disappointing. Many cardioprotective strategies act through common end-effectors and may be suboptimal in patients with comorbidities. Melatonin is a pleiotropic molecule with several functions. Its potential to protect the heart against ischemia/reperfusion damage has attracted much attention, particularly in view of its possible clinical applications. In this brief overview, we discuss the possible clinical application of melatonin in human.

Acute myocardial infarction complicating ischemic stroke: is there room for cangrelor?

Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.