Pathogenesis Of Acute Myocardial Infarction Research Articles

CircDiaph3 aggravates H/R-induced cardiomyocyte apoptosis and inflammation through miR-338-3p/SRSF1 axis

Acute myocardial infarction (AMI) is one of the most prevalent cardiovascular diseases, accounting for a high incidence rate and high mortality worldwide. Hypoxia/reoxygenation (H/R)-induced myocardial cell injury is the main cause of AMI. Several studies have shown that circular RNA contributes significantly to the pathogenesis of AMI. Here, we established an AMI mouse model to investigate the effect of circDiaph3 in cardiac function and explore the functional role of circDiaph3 in H/R-induced cardiomyocyte injury and its molecular mechanism. Bioinformatics tool and RT-qPCR techniques were applied to detect circDiaph3 expression in human patient samples, heart tissues of AMI mice, and H/R-induced H9C2 cells. CCK-8 was used to examine cell viability, while annexin-V/PI staining was used to assess cell apoptosis. Myocardial reactive oxygen species (ROS) levels were detected by immunofluorescence. Western blot was used to detect the protein expression of anti-apoptotic Bcl-2 while pro-apoptotic Bax and cleaved-Caspase-3. Furthermore, ELISA was used to detect inflammatory cytokines production. While bioinformatics tool and RNA pull-down assay were used to verify the interaction between circDiaph3 and miR-338-3p. We found that circDiaph3 expression was high in AMI patients and mice, as well as in H/R-treated H9C2 cells. CircDiaph3 silencing ameliorated apoptosis and inflammatory response of cardiomyocytes in vivo. Moreover, the knockdown of cirDiaph3 mitigated H/R-induced apoptosis and the release of inflammatory mediators like IL-1β, IL-6, and TNF-α in H9C2 cells. Mechanistically, circDiaph3 induced cell apoptosis and inflammatory responses in H/R-treated H9C2 cells by sponging miR-338-3p. Overexpressing miR-338-3p in H/R-treated cells prominently reversed circDiaph3-induced effects. Notably, miR-338-3p inhibited SRSF1 expression in H/R-treated H9C2 cells. While overexpressing SRSF1 abrogated miR-338-3p-mediated alleviation of apoptosis and inflammation after H/R treatment. To summarize, circDiaph3 aggravates H/R-induced cardiomyocyte apoptosis and inflammation through the miR-338-3p/SRSF1 axis. These findings suggest that the circDiaph3/miR-338-3pp/SRSF1 axis could be a potential therapeutic target for treating H/R-induced myocardial injury.

Serum myeloperoxidase, paraoxonase, and plasma asprosin concentrations in patients with acute myocardial infarction

IntroductionThe objective of this study was to evaluate the usefulness of the serum biomarkers myeloperoxidase (MPO), paraoxonase (PON), and plasma asprosin in acute myocardial infarction (AMI) diagnosis and assess their compatibility with routinely screened cardiac biomarkers. MethodsThis study was conducted using a prospective cross-sectional design and included 90 patients, consisting of 60 patients diagnosed with AMI (30 with ST-segment elevation and 30 with non-ST-segment elevation on ECG) and 30 controls (without a diagnosis of AMI). Changes in the levels of cardiac biomarkers (Hs-cTnI, CK, CK-MB), lipid profile (TC, TG, LDL, HDL), MPO, PON, asprosin, and routine biochemical parameters of patients were evaluated. Furthermore, receiver operating characteristic curve analysis revealed the diagnostic value of Hs-cTnI, MPO, PON, and asprosin in predicting AMI. Binary logistic regression analysis of cardiac marker concentrations was used to predict the presence of AMI. In contrast, multinomial logistic regression analysis was conducted to predict the type of AMI and the control group. ResultsThe median levels of MPO and plasma asprosin were found to be higher in the patient group (3.22 [interquartile range {IQR}: 2.4–4.4] ng/ml and 10.84 [IQR: 8.8–17.8] ng/ml, respectively) than in the control group (2.49 [IQR: 1.9–2.9] ng/ml and 4.82 [IQR: 4.6–8.0] ng/ml, respectively) (p = 0.001 and p < 0.001, respectively). The median levels of PON were 8.94 (IQR: 7.6–10.4) ng/ml in the patient group and 10.44 (IQR: 9.1–20.0) ng/ml in the control group (p < 0.001). In the binary logistic regression model, compared with the control group, a 1 ng/ml increase in MPO level increased the odds of having AMI by 3.61 (p = 0.041, 95% CI: 1.055–12.397), whereas a 1 ng/ml increase in asprosin level increased the odds of having AMI by 2.33 (p < 0.001, 95% CI: 1.479–3.683). In the multinominal logistic regression model, compared with the control group, a 1 ng/ml increase in the MPO level increased the odds of having NSTEMI by 4.14 (p = 0.025, 95% CI: 1.195–14.350), whereas a 1 ng/ml increase in asprosin concentrations increased the odds of having NSTEMI by 2.35 (p < 0.001, 95% CI: 1.494–3.721). ConclusionHerein, MPO and asprosin concentrations increased with Hs-cTnI, and a decrease in PON concentration indicated that oxidant–antioxidant parameters and adipokines were related to AMI pathogenesis.

THE ROLE OF NEUTROPHILS TO LYMPHOCYTES RATIO AS PREDICTIVE BIOMARKER IN ACUTE MYOCARDIAL INFARCTION PATIENTS AT AL-GAMHURIA MODERN GENERAL HOSPITAL – ADEN-YEMEN

Inflammation plays a fundamental role in the development of atherosclerosis and in the pathogenesis of acute myocardial infarction (AMI). Neutrophils to lymphocytes ratio (NLR) was recognized as important inflammatory marker in predicting the severity and prognosis of AMI. The aim of this study is to determine the role of NLR as predictive biomarker in AMI patients at Al-Gamhuria Modern General Hospital. This study was considered a descriptive cross-sectional study, which was conducted in Al-Gamhuria Modern General Hospital from March through August 2022. The study includes 124 patients diagnosed as AMI and classified into two groups: 70 patients with low NLR and 54 patients with high NLR. Out of 124 patients, 56.5% of patients had low NLR and 43.5% had high NLR. Patients with high NLR were older (62.31 ± 7.30 vs. 57.80 ± 5.17 years), had higher prevalence of D.M., hyperlipidemia, more smokers and Khat chewers compared to patients with low NLR. High NLR group had more elevated CK-MB and Troponin T, more reduced ejection fraction (EF) and fractional shortening (FS) compared to low NLR group (P &lt; 0.001). High NLR group also had poorer Killip class (P &lt; 0.001), and were more prone to death inside the hospital compared to low NLR group (11.1% vs. 1.4%), (P= 0.042). As conclusion, NLR is a strong predictor of myocardial damage, myocardial dysfunction as well as in-hospital mortality in patients with AMI. NLR as an inflammatory marker can also predict the consequences on the heart post-MI.

Evaluation of Prognostic Significance of Serum Magnesium Level in Patients with Acute Myocardial Infarction

Background: Magnesium has been considered an important factor in the pathogenesis of acute myocardial infarction and its complications. Magnesium ions are essential for the maintenance of the functional integrity of the myocardium. It also improves vascular tone, afterload and cardiac output, and decreases peripheral vascular resistance and cardiac arrhythmias. Serum magnesium concentration has great significance in the prognosis of acute myocardial infarction (MI). Aim and objective: This study aimed to assess the relation of low serum magnesium levels with post-infarction complications of acute MI. Methods: This cross-sectional descriptive study was conducted in the Department of Pharmacology &amp; Therapeutics, Rajshahi Medical College in collaboration with the Cardiology department between July 2019 to June 2020. Assessment and comparison of the serum magnesium level of the patients on the 5th day of post-infarction with the 1st day of admission in 50 patients of acute MI was done in this study. Results: The mean magnesium level was 2.25 ± 0.15 mg/dl in patients without any complications which was significantly higher than the patients who had multiple complications. The level of magnesium was 1.79 ± 0.37 mg/dl in complicated cases. (P˂0.001). These observations suggest that in acute myocardial infarction, patients with low magnesium levels are more prone to develop complications. Conclusion: So it can be concluded that measurement of serum magnesium levels has prognostic significance and magnesium treatment can be implicated in patients of acute myocardial infarction with low magnesium levels. Mediscope 2024;11(1): 27-33

Analysis of immunoinfiltration and EndoMT based on TGF-β signaling pathway-related genes in acute myocardial infarction

Acute myocardial infarction (AMI), a critical manifestation of coronary heart disease, presents a complex and not entirely understood etiology. This study investigates the potential role of immune infiltration and endothelial-mesenchymal transition (EndoMT) in AMI pathogenesis. We conducted an analysis of the GSE24519 and MSigDB datasets to identify differentially expressed genes associated with the TGF-β signaling pathway (DE-TSRGs) and carried out a functional enrichment analysis. Additionally, we evaluated immune infiltration in AMI and its possible link to myocardial fibrosis. Key genes were identified using machine learning and LASSO logistic regression. The expression of MEOX1 in the ventricular muscles and endothelial cells of Sprague–Dawley rats was assessed through RT-qPCR, immunohistochemical and immunofluorescence assays, and the effect of MEOX1 overexpression on EndoMT was investigated. Our study identified five DE-TSRGs, among which MEOX1, SMURF1, and SPTBN1 exhibited the most significant associations with AMI. Notably, we detected substantial immune infiltration in AMI specimens, with a marked increase in neutrophils and macrophages. MEOX1 demonstrated consistent expression patterns in rat ventricular muscle tissue and endothelial cells, and its overexpression induced EndoMT. Our findings suggest that the TGF-β signaling pathway may contribute to AMI progression by activating the immune response. MEOX1, linked to the TGF-β signaling pathway, appears to facilitate myocardial fibrosis via EndoMT following AMI. These novel insights into the mechanisms of AMI pathogenesis could offer promising therapeutic targets for intervention.

Identification of key biomarkers for predicting CAD progression in inflammatory bowel disease via machine-learning and bioinformatics strategies.

The study aimed to identify the biomarkers for predicting coronary atherosclerotic lesions progression in patients with inflammatory bowel disease (IBD). Related transcriptome datasets were seized from Gene Expression Omnibus database. IBD-related modules were identified via Weighted Gene Co-expression Network Analysis. The 'Limma' was applied to screen differentially expressed genes between stable coronary artery disease (CAD) and acute myocardial infarction (AMI). Subsequently, we employed protein-protein interaction (PPI) network and three machine-learning strategies to further screen for candidate hub genes. Application of the receiver operating characteristics curve to quantitatively evaluate candidates to determine key diagnostic biomarkers, followed by a nomogram construction. Ultimately, we performed immune landscape analysis, single-gene GSEA and prediction of target-drugs. 3227 IBD-related module genes and 570 DEGs accounting for AMI were recognized. Intersection yielded 85 shared genes and mostly enriched in immune and inflammatory pathways. After filtering through PPI network and multi-machine learning algorithms, five candidate genes generated. Upon validation, CTSD, CEBPD, CYP27A1 were identified as key diagnostic biomarkers with a superior sensitivity and specificity (AUC > 0.8). Furthermore, all three genes were negatively correlated with CD4+ T cells and positively correlated with neutrophils. Single-gene GSEA highlighted the importance of pathogen invasion, metabolism, immune and inflammation responses during the pathogenesis of AMI. Ten target-drugs were predicted. The discovery of three peripheral blood biomarkers capable of predicting the risk of CAD proceeding into AMI in IBD patients. These identified biomarkers were negatively correlated with CD4+ T cells and positively correlated with neutrophils, indicating a latent therapeutic target.

Potential biomarkers of acute myocardial infarction based on the composition of the blood microbiome

BackgroundIt is difficult to distinguish between acute myocardial infarction (AMI) and unstable angina (UA) due to their similar clinical features. In recent years, studies have shown that microbiomes have great potential in distinguishing diseases. The purpose of this study is to describe the composition of serum microbiome in the AMI and UA by 16S rDNA sequencing. MethodsBased on the high-throughput detection platform and 16S rDNA amplification sequencing technology, this study detected the blood microbial composition of 55 patients with AMI and 62 patients with UA. Alpha diversity and Beta diversity analysis were used to compare the differences in microbial composition and bacterial colony structure between AMI and UA groups. We perform PCoA (Principal Co-ordinates Analysis) based on Unweighted Unifrac distance. In addition, various statistical methods were employed to examine the significance of differences in microbial composition and genus between the two groups. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was employed to predict KEGG (Kyoto Encyclopedia of Genes and Genomes) function from 16S sequencing data. Random forest was applied to identify biomarkers and construct the diagnostic model. Subsequently, the stability of the model was verified by 10-fold cross and the diagnostic effectiveness was evaluated through ROC (Receiver Operating Characteristic). ResultsIn this study, we found that alpha diversity index of serum microbiome in AMI group was significantly higher than in UA group. T-test analysis demonstrated that the UA group presented a higher abundance of Ralstonia, Faecalibaculum and Gammaproteobacteria, while Bacteroides, Sphingomonas, Faecalibaculum, Haemophilus, Serratia, Bifidobacterium and Chloroplast were more abundant in the AMI group. The LefSe (LDA Effect Size) analysis showed that the Gammaproteobacteria, Proteobacteria, Ralstonia pickettli, Ralstonia, Burkholderiaceae and Burkholderiales were enriched in UA group, and Bacteroidales, Bacteroidia, Bacteroidota, Clostridia and Firmicutes were more abundant in the AMI group. Ten bacterial diagnostic models were constructed in the random forest. The area under the curve (AUC) in the training set was 88.01%, and the AUC value in the test set was 95.04%. ConclusionIn this study, the composition of blood microorganisms in the groups of patients with AMI and UA has been analyzed, providing novel insights for understanding the pathogenesis of AMI; Blood microbiome may serve as novel diagnostic biomarkers of AMI.

NLRP3 inflammasome in the pathogenesis of acute myocardial infarction: a cardiologist's view

Within five years after myocardial infarction (MI), a third of patients have secondary major adverse cardiovascular events (MACEs). The first randomized clinical trials to show the effectiveness of anti-inflammatory strategies in the prevention of MACEs are CANTOS, COLCOT and LoDoCo2. These studies have identified an effective therapeutic target — the NLRP3 inflammasome. The results of COLCOT and LoDoCo2 led to colchicine becoming the first anti-inflammatory drug to be included in clinical guidelines for the treatment of patients with coronary artery disease (CAD). However, considering colchicine in routine clinical practice requires the cardiologist to have knowledge of the basic molecular mechanisms of inflammation in cardiovascular diseases. The review discusses current data on inflammation and the NLRP3 inflammasome in the pathogenesis of CAD and MI, results and issues of their application in clinical cardiology.

CircUBAP2 ameliorates hypoxia-induced acute myocardial injury by competing with miR-148b-3p and mediating CDKN1B expression

BackgroundA recent high-throughput sequencing study revealed an anomalous underexpression of circular RNA UBAP2 (circUBAP2) in acute myocardial infarction (AMI), yet its biological function within this context remains elusive. This study aims to unravel whether circUBAP2 is instrumental in modulating the pathogenesis of AMI and to illuminate the underlying molecular mechanisms at play. ResultscircUBAP2 was abnormally low expressed in AMI. Inducing circUBAP2 ameliorated hypoxia-induced myocardial cell injury by enhancing cellular viability, and decreasing lactate dehydrogenase release, apoptosis, inflammation, and oxidative damage. circUBAP2 targeted miR-148b-3p, miR-148b-3p overexpression offset circUBAP2-induced cardioprotection. Cyclin-dependent kinase inhibitor 1B (CDKN1B) was mediated by miR-148b-3p, and CDKN1B upregulation suppressed the deleterious effect of circUBAP2 silencing on hypoxic AC16 cells. In addition, overexpression of circUBAP2 improved myocardial injury, decreased myocardial cell apoptosis, and alleviated inflammation and oxidative stress in AMI mice. ConclusionscircUBAP2 ameliorates AMI by competitively binding to miR-148b-3p and mediating CDKN1B expression.How to cite: Li F, Xu L, Ou J, et al. circUBAP2 ameliorates hypoxia-induced acute myocardial injury by competing with miR-148b-3p and mediating CDKN1B expression. Electron J Biotechnol 2024;68. https://doi.org/10.1016/j.ejbt.2023.11.003.

Smoking, immunity, and cardiovascular prognosis: a study of plasma IgE concentration in patients with acute myocardial infarction.

Immunoglobulin E (IgE) is implicated in the pathogenesis of acute myocardial infarction (AMI), and smokers often exhibit elevated plasma IgE levels. However, it remains uncertain whether the role of smoking in the development and prognosis of AMI is influenced by IgE levels. This study aimed to investigate the potential contribution of IgE in mediating the association between smoking and AMI. We conducted a prospective study involving 348 consecutive patients with chest discomfort who underwent coronary angiography. Plasma cotinine, an alkaloid present in tobacco, and IgE levels were measured. The patients were followed up for mean 39-months to assess their long-term prognosis based on major adverse cardiac and cerebrovascular events (MACCE). Our findings indicate that patients with AMI had higher plasma levels of cotinine and IgE. Univariate analyses demonstrated a positive association between plasma cotinine (OR = 1.7, 95% CI: 1.27-2.26, P < 0.001) and IgE (OR = 2.8, 95% CI: 1.75-4.39, P < 0.001) with AMI. Receiver operating characteristics analyses showed that the combined use of cotinine and IgE (AUC: 0.677) had a larger predictive performance compared to cotinine alone (AUC: 0.639) or IgE alone (AUC: 0.657), although the improvement did not reach statistical significance. Multivariable logistic regression revealed a positive association between plasma cotinine and AMI (OR = 1.70, 95% CI: 1.04-2.78, P = 0.036). Furthermore, the inclusion of plasma IgE in the regression model led to a decrease in the OR and 95% CI of plasma cotinine (OR = 1.66, 95% CI: 1.01-2.73, P = 0.048). Process mediation analyses showed a significant indirect effect of plasma cotinine on AMI mediated through increased plasma IgE. Kaplan-Meier analysis during a mean 39-months follow-up revealed that higher plasma levels of IgE were associated with an increased risk of MACCE following AMI (P = 0.047). However, in the context of the COX regression analysis, no significant correlation was observed between IgE, cotinine and AMI. Cotinine exhibits a positive association with AMI, wherein IgE plays a mediating role. Elevated plasma levels of IgE was positively associated with AMI and poor prognosis, which further confirms the adverse role of smoking on the incidence of AMI and prognosis. (Clinical trial registration: ChiCTR2100053000).

Identification of Immuno-Inflammation-Related Biomarkers for Acute Myocardial Infarction Based on Bioinformatics.

Previous studies have confirmed that inflammation and immunity are involved in the pathogenesis of acute myocardial infarction (AMI). However, only few related genes are identified as biomarkers for the diagnosis and treatment of AMI. GSE48060 and GSE60993 datasets were retrieved from Gene Expression Omnibus. The differentially expressed immuno-inflammation-related genes (DEIIRGs) were obtained from GSE48060, and the biomarkers for AMI were screened and validated using the "Neuralnet" package and GSE60993 dataset. Further, the biomarker-based nomogram was constructed, and miRNAs, transcription factors (TFs), and potential drugs targeting the biomarkers were explored. Furthermore, immune infiltration analysis was analyzed in AMI. Finally, the biomarkers were verified by assessing their mRNA levels using real-time quantitative PCR (RT-qPCR). First, eight biomarkers were screened via bioinformatics, and the artificial neural network model indicated a higher prediction accuracy for AMI even in the validation dataset. Nomogram had accurate forecasting ability for AMI as well. The TFs GTF2I, PHOX2B, RUNX1, and FOS targeting hsa-miR-1297 could regulate the expressions of ADM and CBLB, and RORA could effectively interact with melatonin and citalopram. RT-qPCR results for ADM, PI3, MMP9, NRG1 and CBLB were consistent with those of bioinformatic analysis. In conclusion, eight key immuno-inflammation-related genes, namely, SH2D1B, ADM, PI3, MMP9, NRG1, CBLB, RORA, and FASLG, may serve as the potential biomarkers for AMI, in which the downregulation of CBLB and upregulation of ADM, PI3, and NRG1 in AMI was detected for the first time, providing a new strategy for the diagnosis and treatment of AMI.

Pretreatment with P2Y12 Receptor Inhibitors in Acute Coronary Syndromes-Is the Current Standpoint of ESC Experts Sufficiently Supported?

Excessive platelet reactivity plays a pivotal role in the pathogenesis of acute myocardial infarction. Today, the vast majority of patients presenting with acute coronary syndromes qualify for invasive treatment strategy and thus require fast and efficient platelet inhibition. Since 2008, in cases of ST-elevation myocardial infarction, the European Society of Cardiology guidelines have recommended pretreatment with a P2Y12 inhibitor. This approach has become the standard of care in the majority of centers worldwide. Nevertheless, the latest guidelines for the management of patients presenting with acute coronary syndrome without persisting ST-elevation preclude routine pretreatment with the P2Y12 receptor inhibitor. Those who oppose pretreatment support their stance with trials failing to prove the benefits of this strategy at the cost of an increased risk of major bleeding, especially in individuals inappropriately diagnosed with an acute coronary syndrome, thus having no indication for platelet inhibition. However, adequate platelet inhibition requires even up to several hours after application of a loading dose of P2Y12 receptor inhibitors. Omission of data from pharmacokinetic and pharmacodynamic studies in the absence of data from clinical studies makes generalization of the pretreatment recommendations difficult to accept. We aimed to review the scientific evidence supporting the current recommendations regarding pretreatment with P2Y12 inhibitors.

Differential Expression of Caveolin-3, Suppression of Tumorigenicity 2, and Growth Differentiation Factor-15 Genes and Their Association with Acute Myocardial Infarction: A Cross-Sectional Study in a Multi-Specialty Hospital in Tamil Nadu

Background: Acute myocardial infarction (AMI) is one of the world's leading causes of cardiovascular death. Recent studies have reported the influence of the genes caveolin-3 (CAV3), suppression of tumorigenicity 2, and growth differentiating factor-15 in cardiovascular diseases, especially myocardial infarction, but their role and function remain unclear. Hence, this study was designed to evaluate the expression levels of these three genes in AMI and understanding the role of CAV-3 in the pathogenesis of AMI. Methods and Results: Blood samples were collected from 50 AMI patients and 50 non-AMI controls in this cross-sectional study. Relative expression levels of the three genes were performed using real-time PCR. Bioinformatics tools were used for functional gene enrichment and protein-protein interactions. CAV-3 was significantly upregulated among AMI patients compared to controls. In silico analyses identified CAV-3 as playing critical roles in smooth muscle contraction, cardiac conduction, and calcium-mediated transport via binding with essential proteins including dysferlin and annexins Conclusion: This study is a first of its kind, reporting an upregulation of CAV-3 in AMI patients. The expression of all three genes significantly influenced the systolic function of the heart in AMI patients. A more in-depth understanding of CAV-3 in the pathophysiology of AMI is essential and it may prove to be a novel.

Role of intestinal microbiocenosis in pathogenesis of acute myocardial infarction

Objective. To study changes in the qualitative and quantitative composition of the microbiome of the gastrointestinal tract as one of the main factors affecting the state of general and local immunity in patients with acute myocardial infarction.Methods. According to the recommendations of the European Society of Cardiology 2019, the cardiological status of the subjects was established. Based on the methodology proposed by the Moscow Research Institute of Epidemiology and Microbiology n. a. G. N. Gabrichevsky, the qualitative and quantitative composition of the intestinal microbiota was determined, followed by an assessment of the degree of microbiological disorders according to the industry standard ‘Protocol of patient management. Intestinal dysbiosis’.Results and conclusions. A bacteriological study revealed a reduction in the main representatives of the normobiota: Bifidobacterium, Eubacterium, Lactobacterium, Enterococcus spp., forming the ‘metabolic core’ of intestinal microbiocenosis. The results obtained are part of a clinical and laboratory study of changes in the microbiota of the body in diseases of the circulatory system and can serve as a basis for developing recommendations for effective treatment and prevention of cardiovascular pathology, taking into account the state of intestinal microbiocenosis.

Machine learning-based integration develops biomarkers initial the crosstalk between inflammation and immune in acute myocardial infarction patients.

Great strides have been made in past years toward revealing the pathogenesis of acute myocardial infarction (AMI). However, the prognosis did not meet satisfactory expectations. Considering the importance of early diagnosis in AMI, biomarkers with high sensitivity and accuracy are urgently needed. On the other hand, the prevalence of AMI worldwide has rapidly increased over the last few years, especially after the outbreak of COVID-19. Thus, in addition to the classical risk factors for AMI, such as overwork, agitation, overeating, cold irritation, constipation, smoking, and alcohol addiction, viral infections triggers have been considered. Immune cells play pivotal roles in the innate immunosurveillance of viral infections. So, immunotherapies might serve as a potential preventive or therapeutic approach, sparking new hope for patients with AMI. An era of artificial intelligence has led to the development of numerous machine learning algorithms. In this study, we integrated multiple machine learning algorithms for the identification of novel diagnostic biomarkers for AMI. Then, the possible association between critical genes and immune cell infiltration status was characterized for improving the diagnosis and treatment of AMI patients.

A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection

Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increased risk of type 1 diabetes mellitus in adults. However, there are no approved vaccines or direct antiviral agents available to prevention or treatment of coxsackievirus infection. Here, we reported that GC376 potently inhibited CV-A10 infection in different cell lines without cytotoxicity, significantly suppressed production of viral proteins, and strongly reduced the yields of infectious progeny virions. Further study indicated that GC376, as viral 3C protease inhibitor, had the potential to restrain the cleavage of the viral polyprotein into individually functional proteins, thus suppressed the replication of CV-A10. Furthermore, the drug exhibited antiviral activity against coxsackieviruses of various serotypes including CV-A6, CV-A7 and CV-A16, suggesting that GC376 is a broad-spectrum anti-coxsackievirus inhibitor and the 3C protease is a promising target for developing anti-coxsackievirus agents.

A Study on the Protective Effect of sRAGE-MSCs in a Rodent Reperfusion Model of Myocardial Infarction

Acute myocardial infarction (AMI) is one of the major leading causes of death in humans globally. Recently, increased levels of recruited macrophages and AGE-albumin were observed in the hearts of humans and animals with acute myocardial infarction. Thus, the purposes of this study were to investigate whether the elevated levels of AGE-albumin from activated macrophage cells are implicated in ischemia-induced cardiomyocyte death and to develop therapeutic strategies for AMI based on its underlying molecular mechanisms with respect to AGEs. The present study demonstrated that activated macrophages and AGE-albumin were observed in heart tissues obtained from humans and rats with AMI incidences. In the cellular model of AMI, it was found that increased expression of AGE-albumin was shown to be co-localized with macrophages, and the presence of AGE-albumin led to increased expression of RAGE through the mitogen-activated protein kinase pathway. After revealing cardiomyocyte apoptosis induced by toxicity of the AGE-RAGE system, sRAGE-secreting MSCs were generated using the CRISPR/Cas9 platform to investigate the therapeutic effects of sRAGE-MSCs in an AMI rat model. Gene-edited sRAGE-MSCs showed greater therapeutic effects against AMI pathogenesis in rat models compared to mock MSCs, and promising results of the functional improvement of stem cells could result in significant improvements in the clinical management of cardiovascular diseases.

Abstract 10285: Prognostic Value of Provocative Spasm Test in Patients With Myocardial Infarction With and Without Obstructive Coronary Arteries

Introduction : Coronary spasm potentially contributes to the pathogenesis of acute myocardial infarction (MI) with obstructive coronary artery disease (MICAD) and particularly warrants close consideration in MI with non-obstructive coronary arteries (MINOCA). However, there are limited data concerning the impact of coronary spasm in acute myocardial infarction (AMI). We aimed to assess the prognostic impact of provocative coronary spasm in both MICAD and MINOCA. Methods: Of 1,101 AMI patients admitted to our hospital from January 2012 to December 2019, 267 AMI patients (MICAD: n=198, MINOCA: n=69) who underwent emergency CAG and invasive provocative spasm test were assessed. The primary endpoint was a composite of major adverse cardiac events (MACE), defined as cardiovascular death, acute coronary syndrome, or revascularization. The median follow-up duration was 48 months. Results: Provocative test was positive in 143 (72.2%) of MICAD group and 33 (47.8%) of MINOCA group. In MICAD group, spasm-positive patients had a significantly higher occurrence of both MACE [27 (18.9%) vs. 4 (7.3%); p=0.0413] and Revascularization [25 (17.5%) vs. 3 (5.5%); p=0.0296] compared to spasm-negative patients. In MINOCA group, MACE occurred only in patients with spasm-positive [4 (12.1%) vs. 0 (0%); p=0.0473]. Among the 4 groups based on the type of MI (MICAD or MINOCA) and the presence of provoked coronary spasm, there was a significant difference in the MACE-free survival rate, with the lowest rate observed for MICAD patients with spasm-positive (log rank P=0.0111). In a Multivariable analysis, provoked coronary spasm was significantly associated with MACE in MICAD group (hazard ratio, 3.37;95% CI, 1.20-12.10; P=0.0189). Conclusions: Provocative spasm test could provide prognostic stratification for AMI patients.

Neutrophils to high-density lipoprotein cholesterol ratio as a new prognostic marker in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a retrospective study

BackgroundNeutrophils and high-density lipoprotein cholesterol (HDL-c) play critical roles in the pathogenesis of acute myocardial infarction. We aimed to investigate the value of neutrophils count to high-density lipoprotein cholesterol ratio (NHR) in predicting occurrence of in-hospital adverse events in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI).MethodsWe retrospectively analyzed 532 patients who had been diagnosed with acute STEMI and treated with PPCI. Demographic and clinical data, admission laboratory parameters and NHR values were recorded. Major adverse cardiac events (MACE) were defined as stent thrombosis, cardiac rupture, cardiac arrest, ventricular aneurysm, malignant arrhythmia and cardiac death. Based on the receiver operating characteristic (ROC) analysis, all patients were divided into 2 groups based on the cut-off NHR value (NHR ≤ 11.28, NHR > 11.28). Cox regression analyses and the Kaplan–Meier survival curve were used to assess the prognostic ability of NHR in in-hospital MACE.ResultsMACE was observed in 72 patients (13.5%) during in-hospital follow-up. NHR was significantly higher in MACE group compared to MACE-free group (10.93 [6.26–13.97] vs. 8.13 [5.89–11.16]; P = 0.001). The incidence of in-hospital MACE was significantly higher in the NHR > 11.28 group than in NHR ≤ 11.28 group (24.8% vs. 9.6%; P < 0.001). In multivariable Cox regression analyses, ALT, Killip III-IV and increased NHR (hazard ratio, 2.211; 95% confidence interval,1.092–4.479; P = 0.027) were identified as independent predictive factors of occurrence of in-hospital MACE. Higher NHR group had worse cumulative survival compared with the lower group.ConclusionsNHR value on admission, which is an easily calculated and universally available maker, may be useful in in-hospital risk classification of STEMI patients undergoing PPCI.

“STUDY ON SERUM MAGNESIUM LEVELS AND INCIDENCE OF ARRHYTHMIAS IN PATIENTS PRESENTING TO EMERGENCY DEPARTMENT WITH ACUTE MYOCARDIAL INFARCTION”

Background; Magnesium has been implicated in the pathogenesis of acute myocardial infarction and its related complication like arrhythmia. Magnesium helps in myocardial metabolism, inhibits calcium accumulation and myocardial cell death. It has role in improving the vascular tone, peripheral vascular resistance, after load and cardiac output, reduces cardiac arrhythmias and improves lipid metabolism. Magnesium reduces vulnerability to oxygen derived free radicals, improves endothelial function and inhibits platelet function including platelet aggregation and adhesion. Objective: To know the relationship between the serum magnesium levels and arrhythmias in patients with acute myocardial infarction.70 cases of acute myocardial infarction, admitted in a tertiary care hospital over a period of 2 years i.e., between October 2015 to October 2017. Results: There is a signicant difference in the magnesium levels in patients with arrhythmias and without arrhythmias. Conclusion: In acute myocardial infarction, patients with low magnesium levels are more prone to get arrhythmias. That is the reason magnesium treatment can be considered in patients of acute myocardial infarction with low magnesium levels.