The association between trimethylamine N-oxide levels and coronary microvascular dysfunction and prognosis in patients with ST-elevation myocardial infarction.

BACKGROUND AND AIMS: Coronary microvascular dysfunction (CMD) is common after ST-elevation myocardial infarction (STEMI), leading to adverse clinical outcomes. However, its diagnosis remains difficult, and mechanisms elusive. This study explores the role of Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, as a potential biomarker for diagnosing CMD in STEMI patients. METHODS: This prospective, observational study enrolled 210 STEMI patients with multivessel coronary artery disease who underwent primary percutaneous coronary intervention (PCI). TMAO levels were measured at baseline, 3 months, and 12 months post-PCI, whilst coronary physiology was assessed at 3 months. The primary endpoint was the incidence of CMD at 3 months, with the secondary endpoint being major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months. An additional 59 consecutive patients were enrolled for validation. RESULTS: TMAO levels varied from baseline to 3 months, then stabilised. The areas under the ROC curve for baseline TMAO and TMAO at 3-month were 0.55 (95 % CI 0.46-0.64; p = 0.426), and 0.80 (95 % CI 0.73-0.87; p < 0.001), respectively. The optimal cut-off for TMAO at 3-month to diagnose CMD was 3.91, with similar sensitivity and specificity in the derivation and validation cohort. The incidence of MACCE was higher in patients with TMAO≥3.91 (41.4 % vs 10.7 %; p < 0.001). The addition of 3-month TMAO improved the diagnostic performance of traditional risk factors. CONCLUSION: TMAO is a robust biomarker for CMD and is significantly associated with the incidence of MACCE. TMAO has the potential in guiding clinical decision-making and suggests an interplay between gut microbiota and CMD.

Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes in Ischemic Heart Failure.

A relevant role of osteopontin (OPN) and gremlin 1 (Grem1) in regulating cardiac tissue remodeling and formation of heart failure (HF) are documented, with the changes of OPN and Grem1 levels in blood plasma due to acute ischemia, ischemic heart disease-induced advanced HF or dilatative cardiomyopathy being the primary focus in most of these studies. However, knowledge on the early OPN and Grem1 proteins expression changes within cardiomyocytes during remodeling due to chronic ischemia remains insufficient. The aim of this study was to determine the OPN and Grem1 proteins expression changes in human cardiomyocytes at different stages of ischemic HF. A semi-quantitative immunohistochemical analysis was performed in 105 myocardial tissue samples obtained from the left cardiac ventricles. Increased OPN immunostaining intensity was already detected in the stage A HF group, compared to the control group (p < 0.001), and continued to increase in the stage B HF (p < 0.001), achieving the peak of immunostaining in the stages C/D HF group (p < 0.001). Similar data of Grem1 immunostaining intensity changes in cardiomyocytes were documented. Significantly positive correlations were detected between OPN, Grem1 expression in cardiomyocytes and their diameter as well as the length, in addition to positive correlation between OPN and Grem1 expression changes within cardiomyocytes. These novel findings suggest that OPN and Grem1 contribute significantly to reorganization of cellular geometry from the earliest stage of cardiomyocyte remodeling, providing new insights into the ischemic HF pathogenesis.

Impact of CYP2C19 Gene Variants on Long-Term Treatment with Atorvastatin in Patients with Acute Coronary Syndromes.

The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve clinical outcomes. Currently, there is a lack of guidelines allowing the prediction of the therapeutic efficacy of lipid-lowering statin therapy. This study aimed to determine the effects of clinically significant gene variants of CYP2C19 on atorvastatin therapy in patients with acute coronary syndromes. In total, 92 patients with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) were sequenced for target regions within the CYP2C19 gene on the Illumina Miniseq system. The CYP2C19 poor metabolizer phenotype (carriers of CYP2C19*2, CYP2C19*4, and CYP2C19*8 alleles) was detected in 29% of patients. These patients had significantly lower responses to treatment with atorvastatin than patients with the normal metabolizer phenotype. CYP2C19-metabolizing phenotype, patient age, and smoking increased the odds of undertreatment in patients (∆LDL-C (mmol/L) < 1). These results revealed that the CYP2C19 phenotype may significantly impact atorvastatin therapy personalization in patients requiring LDL lipid-lowering therapy.

Effects of Combined Treatment with Sodium Dichloroacetate and Sodium Valproate on the Genes in Inflammation- and Immune-Related Pathways in T Lymphocytes from Patients with SARS-CoV-2 Infection with Pneumonia: Sex-Related Differences.

The study presents data on the anti-inflammatory effects of a combination of sodium dichloroacetate and sodium valproate (DCA-VPA) on the expression of inflammation- and immune response-related genes in T lymphocytes of SARS-CoV-2 patients. The study aimed to assess the effects of DCA-VPA on the genes of cytokine activity, chemokine-mediated signaling, neutrophil chemotaxis, lymphocyte chemotaxis, T-cell chemotaxis, and regulation of T-cell proliferation pathways. The study included 21 patients with SARS-CoV-2 infection and pneumonia: 9 male patients with a mean age of 68.44 ± 15.32 years and 12 female patients with a mean age of 65.42 ± 15.74 years. They were hospitalized between December 2022 and March 2023. At the time of testing, over 90% of sequences analyzed in Lithuania were found to be of the omicron variant of SARS-CoV-2. The T lymphocytes from patients were treated with 5 mmol DCA and 2 mmol VPA for 24 h in vitro. The effect of the DCA-VPA treatment on gene expression in T lymphocytes was analyzed via gene sequencing. The study shows that DCA-VPA has significant anti-inflammatory effects and apparent sex-related differences. The effect is more potent in T cells from male patients with SARS-CoV-2 infection and pneumonia than in females.

Enterobacterales Biofilm-Specific Genes and Antimicrobial and Anti-Inflammatory Biomarkers in the Blood of Patients with Ischemic Heart Disease.

BACKGROUND: Ischemic heart disease (IHD) is the most prevalent type of cardiovascular disease. The main cause of IHD is atherosclerosis, which is a multifactorial inflammatory disease of blood vessels. Studies show that bacteria might have a significant impact on the pathogenesis of atherosclerosis and plaque rupture. This study aimed to evaluate the complexity of interactions between bacteria and the human body concerning metabolites and bacterial genes in patients with ischemic heart disease. METHODS: Bacterial 16S rDNA and wcaF, papC, and sdhC genes were detected in whole blood using a real-time PCR methodology. An enzyme-linked immunosorbent assay was used to measure the concentration of the LL-37 protein. An analysis of ARA in blood plasma was performed. RESULTS: Bacterial 16S rDNA was detected in 31% of the study patients, and the genes wcaF and sdhC in 20%. Enterobacterales genes were detected more frequently in patients younger than 65 years than in patients aged 65 years and older (p = 0.018) and in patients with type 2 diabetes (p = 0.048). Concentrations of the human antimicrobial peptide LL-37 and 12S-HETE concentrations were determined to be higher if patients had 16S rDNA and biofilm-specific genes. CONCLUSIONS: The results of this study enhance the understanding that Enterobacterales bacteria may participate in the pathogenesis of atherosclerosis and IHD. Bacterial DNA and host metabolites in higher concentrations appear to be detected.

The Effect of Platelet Activity, ABCB1 Genetic Polymorphism, and Renal Function on the Development of Ticagrelor-Related Dyspnea in Patients with Acute Coronary Syndrome.

Purpose: The aim of this study was to determine the effect of ABCB1 genetic polymorphism and renal function on the occurrence of ticagrelor-related dyspnea. Patients and Methods: A total of 299 patients with acute with type 1, 2, or 3 myocardial infarction (with and without ST-segment elevation), who underwent coronary angiography and PTCA with stent implantation and were treated with antiplatelet drugs (ticagrelor and aspirin), were enrolled in this prospective study. For all enrolled patient's platelet aggregation (induction with high-sensitivity adenosine diphosphate, ADP HS) testing was performed using a MULTIPLATE® analyzer. Venous blood was also collected for genotyping. Results: Patients experiencing ticagrelor-related dyspnea had lower ADP HS value (ADP HS ≤ 19.5 U; OR = 2.254; P = 0.009), higher creatinine concentration (>90 µmol/l; OR = 3.414; P = 0.019), and lower GFR value (<60 mL/min/1.73 m2; OR = 2.211; P = 0.035). ABCB1 T allele was associated with ticagrelor-related dyspnea (OR = 2.550; P = 0.04). Conclusion: Ticagrelor-related dyspnea was found to be related to low platelet aggregation, increased plasma creatinine concentration, decreased GFR, and ABCB1 T allele. Carriers of the ABCB1 T allele had a higher plasma creatinine concentration that could be associated with an inhibitory effect of ticagrelor on P-glycoprotein function.

Coronary artery disease, its associations with ocular, genetic and blood lipid parameters.

BACKGROUND/OBJECTIVES: To investigate the associations between ophthalmic parameters, CYP4F2 (rs2108622) and ABCA1 (rs1883025) polymorphisms and coronary artery disease, considering the accessibility, non-invasive origin of retinal examination and its possible resemblance to coronary arteries. SUBJECTS/METHODS: Overall 165 participants divided into groups based on the coronary angiography results and clinical status: control group (N = 73), MI group (N = 63), 3VD (three vessel disease) (N = 24). All the participants underwent total ophthalmic examination - optical coherence tomography (OCT) and OCT angiography of the macula region were performed and evaluated. Total cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride cholesterol (Tg-C) were tested. A standard manufacturer's protocol for CYP4F2 (rs2108622) and ABCA1 (rs1883025) was used for genotyping with TaqMan probes. RESULTS: GCL+ layer was thicker in control group vs. 3VD group (74.00; 62.67-94.67 (median; min.-max.) vs. 71.06; 51.33-78.44, p = 0.037). T allele carriers under ABCA1 rs1883025 dominant model were shown to have ticker retina and smaller foveal avascular zone in superficial capillary plexus and smaller Tg-C concentration. ABCA1 rs1883025 was associated with retinal thickness (OR = 0.575, 95% CI 0.348-0.948, p = 0.030). Univariate logistic regression showed that ABCA1 rs1883025 CT genotype is associated with decreased risk for coronary artery disease development under overdominant genetic model (OR = 0.498, 95% CI 0.254-0.976; p = 0.042) and codominant genetic model (OR = 0.468, 95% CI 0.232-0.945, p = 0.034). CONCLUSIONS: Results of this study confirmed that non-invasive methods such as OCT of eye might be used for identification of patients at risk of CAD.

Preclinical Study in Mouse Thymus and Thymocytes: Effects of Treatment with a Combination of Sodium Dichloroacetate and Sodium Valproate on Infectious Inflammation Pathways.

The research presents data from a preclinical study on the anti-inflammatory effects of a sodium dichloroacetate and sodium valproate combination (DCA-VPA). The 2-week treatment with a DCA 100 mg/kg/day and VPA 150 mg/kg/day combination solution in drinking water's effects on the thymus weight, its cortex/medulla ratio, Hassall's corpuscles (HCs) number in the thymus medulla, and the expression of inflammatory and immune-response-related genes in thymocytes of male Balb/c mice were studied. Two groups of mice aged 6-7 weeks were investigated: a control (n = 12) and a DCA-VPA-treated group (n = 12). The treatment did not affect the body weight gain (p > 0.05), the thymus weight (p > 0.05), the cortical/medulla ratio (p > 0.05), or the number of HCs (p > 0.05). Treatment significantly increased the Slc5a8 gene expression by 2.1-fold (p < 0.05). Gene sequence analysis revealed a significant effect on the expression of inflammation-related genes in thymocytes by significantly altering the expression of several genes related to the cytokine activity pathway, the inflammatory response pathway, and the Il17 signaling pathway in thymocytes. Data suggest that DCA-VPA exerts an anti-inflammatory effect by inhibiting the inflammatory mechanisms in the mouse thymocytes.

Remodeling of Cardiomyocytes: Study of Morphological Cellular Changes Preceding Symptomatic Ischemic Heart Failure.

Although major pathogenesis mechanisms of heart failure (HF) are well established, the significance of early (mal)adaptive structural changes of cardiomyocytes preceding symptomatic ischemic HF remains ambiguous. The aim of this study is to present the morphological characterization of changes in cardiomyocytes and their reorganization of intermediate filaments during remodeling preceding symptomatic ischemic HF in an adult human heart. A total of 84 myocardial tissue samples from middle-left heart ventricular segments were analyzed histomorphometrically and immunohistochemically, observing the cardiomyocyte's size, shape, and desmin expression changes in the remodeling process: Stage A of HF, Stage B of HF, and Stages C/D of HF groups (ACC/AHA classification). Values p < 0.05 were considered significant. The cellular length, diameter, and volume of Stage A of HF increased predominantly by the diameter vs. the control group (p < 0.001) and continued to increase in Stage B of HF in a similar pattern (p < 0.001), increasing even more in the C/D Stages of HF predominantly by length (p < 0.001). Desmin expression was increased in Stage A of HF vs. the control group (p < 0.001), whereas it was similar in Stages A and B of HF (p > 0.05), and most intense in Stages C/D of HF (p < 0.001). Significant morphological changes of cardiomyocytes and their cytoskeletal reorganization were observed during the earliest remodeling events preceding symptomatic ischemic HF.

Associations of the serotonin transporter gene polymorphism, 5-HTTLPR, and adverse life events with late life depression in the elderly Lithuanian population.

Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65 years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6 months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression.

Artificial intelligence for automated evaluation of aortic measurements in 2D echocardiography: Feasibility, accuracy, and reproducibility.

AIMS: This study sought to examine the feasibility, accuracy and reproducibility of a novel, fully automated 2D transthoracic echocardiography (2D TTE) parasternal long axis (PLAX) view aortic measurements quantification software compared to board-certified cardiologists in controlled clinical setting. METHODS AND RESULTS: Aortic Annulus (AoA), Aortic Sinus (AoS), Sinotubular Junction (STJ) and Proximal Ascending Aorta (AAo) diameter measurements were performed retrospectively on each of 58 subjects in two different ways: twice using a fully automated software (Ligence Heart version 2) and twice manually by three cardiologists (ORG) and one expert cardiologist (EC). Out of 58 studies AoA was measured in 54 (93%), AoS in 55 (95%), STJ in 55 (95%) and AAo in 54 (93%) studies. Automated measurements had a stronger correlation with EC when compared to ORG with the largest correlation difference of .1 for STJ measurements and lowest difference of .01 for AoS measurements. Automated software was in higher agreement with ground truth intervals (ORG measurements mean +- SEM) in three out of four measurements. CONCLUSION: Fully automated 2D TTE PLAX view aortic measurements using a novel AI-based quantification software are feasible and yield results that are in close agreement with what experienced readers measure manually while providing better reproducibility. This approach may prove to have important clinical implications in the automation of the aortic root and ascending aorta assessment to improve workflow efficiency.

The Comparative Experimental Study of Sodium and Magnesium Dichloroacetate Effects on Pediatric PBT24 and SF8628 Cell Glioblastoma Tumors Using a Chicken Embryo Chorioallantoic Membrane Model and on Cells In Vitro.

In this study, pyruvate dehydrogenase kinase-1 inhibition with dichloroacetate (DCA) was explored as an alternative cancer therapy. The study's aim was to compare the effectiveness of NaDCA and MgDCA on pediatric glioblastoma PBT24 and SF8628 tumors and cells. The treatment effects were evaluated on xenografts growth on a chicken embryo chorioallantoic membrane. The PCNA, EZH2, p53, survivin expression in tumor, and the SLC12A2, SLC12A5, SLC5A8, CDH1, and CDH2 expression in cells were studied. The tumor groups were: control, cells treated with 10 mM and 5 mM of NaDCA, and 5 mM and 2.5 mM of MgDCA. The cells were also treated with 3 mM DCA. Both the 10 mM DCA preparations significantly reduced PBT24 and SF8624 tumor invasion rates, while 5 mM NaDCA reduced it only in the SF8628 tumors. The 5 mM MgDCA inhibited tumor-associated neoangiogenesis in PBT24; both doses of NaDCA inhibited tumor-associated neoangiogenesis in SF8628. The 10 mM DCA inhibited the expression of markers tested in PBT24 and SF8628 tumors, but the 5 mM DCA affect on their expression depended on the cation. The DCA treatment did not affect the SLC12A2, SLC12A5, and SLC5A8 expression in cells but increased CDH1 expression in SF8628. The tumor response to DCA at different doses indicated that a contrast between NaDCA and MgDCA effectiveness reflects the differences in the tested cells' biologies.

Pleiotropic Effects of Ticagrelor: Influence on CYP4F2 Gene and Protein Expression in HUVEC and HepG2, and Escherichia coli Bacterial Survival.

Background: Antiplatelet drugs, such as ticagrelor, which target platelet P2Y12 receptors, are used for prevention of ischemic heart disease. Ticagrelor is also known to have pleiotropic effects of unknown mechanisms. Ticagrelor could influence the expression of molecules involved in resolution of inflammation. This study aimed to investigate if ticagrelor could change the expression of CYP4F2 and its encoded protein concentration and, additionally, to determine ticagrelor possible antibacterial activity against gram-negative bacteria. Methods: CYP4F2 expression was determined in HUVEC and HepG2 cell lines by qPCR. CYP4F2 protein concentration was determined by ELISA. Antibiotic susceptibility testing was performed using a disc diffusion method. Results: Ticagrelor was observed to reduce the expression of CYP4F2 in HUVEC and HepG2 cell lines. It also reduced CYP4F2 protein levels in HUVEC cells. Ticagrelor had no bactericidal activity against gram-negative third generation cephalosporin resistant E. coli. Conclusion: Ticagrelor reduced CYP4F2 protein concentration in HUVEC, and CYP4F2 expression in HUVEC and HepG2 cells, but had no effect on third-generation cephalosporin-resistant E. coli strains.

Determining the International Spread of B.1.1.523 SARS-CoV-2 Lineage with a Set of Mutations Highly Associated with Reduced Immune Neutralization.

Here, we report the emergence of the variant lineage B.1.1.523 that contains a set of mutations including 156_158del, E484K and S494P in the spike protein. E484K and S494P are known to significantly reduce SARS-CoV-2 neutralization by convalescent and vaccinated sera and are considered as mutations of concern. Lineage B.1.1.523 presumably originated in the Russian Federation and spread across European countries with the peak of transmission in April-May 2021. The B.1.1.523 lineage has now been reported from 31 countries. In this article, we analyze the possible origin of this mutation subset and its immune response using in silico methods.

SARS-CoV-2: Two Years in the Pandemic: What Have We Observed from Genome Sequencing Results in Lithuania?

SARS-CoV-2 has spread vastly throughout the word. In this study, we focus on the patterns of spread in Lithuania. By analysing the genetically sequenced data of different lineages and their first appearances, we were able to compare the dynamics of spreading of the lineages and recognize the main possible cause. The impact of emigration patterns and international travel on the variety of lineages was also assessed. Results showed different patterns of spread, and while a vast variety of different lineages were brought in by international travel, many of the viral outbreaks were caused by local lineages. It can be concluded that international travel had the most impact on the spread of SARS-CoV-2.

SARS-CoV-2 Infection, Sex-Related Differences, and a Possible Personalized Treatment Approach with Valproic Acid: A Review.

Sex differences identified in the COVID-19 pandemic are necessary to study. It is essential to investigate the efficacy of the drugs in clinical trials for the treatment of COVID-19, and to analyse the sex-related beneficial and adverse effects. The histone deacetylase inhibitor valproic acid (VPA) is a potential drug that could be adapted to prevent the progression and complications of SARS-CoV-2 infection. VPA has a history of research in the treatment of various viral infections. This article reviews the preclinical data, showing that the pharmacological impact of VPA may apply to COVID-19 pathogenetic mechanisms. VPA inhibits SARS-CoV-2 virus entry, suppresses the pro-inflammatory immune cell and cytokine response to infection, and reduces inflammatory tissue and organ damage by mechanisms that may appear to be sex-related. The antithrombotic, antiplatelet, anti-inflammatory, immunomodulatory, glucose- and testosterone-lowering in blood serum effects of VPA suggest that the drug could be promising for therapy of COVID-19. Sex-related differences in the efficacy of VPA treatment may be significant in developing a personalised treatment strategy for COVID-19.

Circulating hsa-let-7e-5p and hsa-miR-125a-5p as Possible Biomarkers in the Diagnosis of Major Depression and Bipolar Disorders.

BACKGROUND: Evidence shows that microRNAs (miRNAs) could play a key role in the homeostasis and development of major depressive disorder and bipolar disorder. The present study is aimed at investigating the changes in circulating miRNA expression profiles in a plasma of patients suffering from major depressive disorder (MDD) and bipolar disorder (BD) to distinguish and evaluate these molecules as biomarkers for mood disorders. METHODS: A study enrolled a total of 184 subjects: 74 controls, 84 MDD patients, and 26 BD patients. Small RNA sequencing revealed 11 deregulated circulating miRNAs in MDD and BD plasma, of which expression of 5, hsa-miR-139-3p, miRNAs hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-125a-5p, and hsa-miR-483-5p, were further verified using qPCR. miRNA gene expression data was evaluated alongside the data from clinical assessment questionnaires. RESULTS: hsa-let-7e-5p and hsa-miR-125a-5p were both confirmed upregulated: 0.75-fold and 0.25-fold, respectively, in the MDD group as well as 1.36-fold and 0.68-fold in the BD group. Receiver operating curve (ROC) analysis showed mediocre diagnostic sensitivity and specificity of both hsa-let-7e-5p and hsa-miR-125a-5p with approximate area under the curve (AOC) of 0.66. ROC analysis of combined miRNA and clinical assessment data showed that hsa-let-7e-5p and hsa-miR-125a-5p testing could improve MDD and BD diagnostic accuracy by approximately 10%. CONCLUSIONS: Circulating hsa-let-7e-5 and hsa-miR-125a-5p could serve as additional peripheral biomarkers for mood disorders; however, suicidal ideation remains the major diagnostic factor for MDD and BD.

Blood direct PCR: impact of CYP2C19 and CYP4F2 variants for bleeding prediction in ST-elevation myocardial infarction patients with ticagrelor.

Aims: The goals of this study were to develop a new technique that could pave the way for a quicker determination of CYP4F2 rs3093135 and CYP2C19 rs4244285 variants directly from a patient's blood and to attempt to apply this technique in clinical practice. Patients & methods: The study included 144 consecutive patients admitted with ST elevation myocardial infarction. A blood-direct PCR and real-time PCR were used to detect variants of interest. Results & conclusion: Patients with bleeding events had the CYP2C19 GG (*1*1) variant more frequently than patients without bleeding events. The CYP4F2 TT variant was more frequently detected in patients with bleeding events 3 months after hospitalization.

Ticagrelor is one of the main antiplatelet drugs used for prevention of coronary blood clots after interventional procedures in patients with acute coronary syndromes. It has previously been shown that gene variants of CYP2C19 and CYP4F2 may affect antiplatelet therapy. This paper reports a novel instrument and the results of genetic tests obtained using this instrument. Our instrument can detect variants of the genes associated with ticagrelor antiplatelet therapy in only 40 min. These findings might facilitate individualized treatment with ticagrelor of patients with ST-elevation myocardial infarction.

Impact of Mineralocorticoid Receptor Gene NR3C2 on the Prediction of Functional Classification of Left Ventricular Remodeling and Arrhythmia after Acute Myocardial Infarction.

Background: The NR3C2 gene encodes the mineralocorticoid receptor, which is present on cardiomyocytes. Prior studies reported an association between the presence of NR3C2 single-nucleotide polymorphisms (SNPs) and an increased cortisol production during a stress response such as acute myocardial infarction (AMI), which may lead to adverse cardiac remodeling. Objective: To study the impact of the NR3C2 rs2070950, rs4635799 and rs5522 gene polymorphisms on left ventricular (LV) remodeling, rhythm and conduction disorders in AMI patients. Methods: A cohort of 301 AMI patients who underwent revascularization was included. SNPs of the NR3C2 gene (rs2070950, rs4635799 and rs5522) were evaluated. A total of 127 AMI patients underwent transthoracic echocardiography follow-up after 72 h and 6 months. Results: The rs2070950 GG genotype and rs4635799 TT genotype were most common in patients who had LV end-diastolic volume increase < 20% and the same or increased LV ejection fraction, indicating a possible protective effect of these SNPs. The rs5522 TT genotype was associated with a higher frequency of arrhythmias, while the presence of at least one rs5522 C allele was associated with a lower risk of arrhythmias. Conclusion: SNPs of the NR3C2 gene appear to correlate with better ventricular remodeling and a reduced rate of arrhythmias post-AMI, possibly by limiting the deleterious effects of cortisol on cardiomyocytes.

Associations of MC4R, LEP, and LEPR Polymorphisms with Obesity-Related Parameters in Childhood and Adulthood.

MC4R, LEP, and LEPR genes are involved in the hypothalamic leptin-melanocortin regulation pathway, which is important for energy homeostasis. Our study aimed to evaluate the associations between the MC4R rs17782313, LEP rs7799039, and LEPR rs1137101 polymorphisms with obesity-related parameters in childhood and adulthood. The data were obtained from the Kaunas Cardiovascular Risk Cohort study, which started in 1977 with 1082 participants aged 12-13 years. In 2012-2014, the follow-up survey was carried out. Genotype analysis of all respondents (n = 509) aged 48-49 years was performed for the gene polymorphisms using Real-Time Polymerase Chain Reaction. Anthropometric measurements were performed in childhood and adulthood. In childhood, only skinfold thicknesses were associated with gene variants being the lowest in children with MC4R TT genotype and LEP AG genotype. In adulthood, odds of obesity and metabolic syndrome was higher in MC4R CT/CC genotype than TT genotype carriers (OR 1.8; 95% CI 1.2-2.8 and OR 1.6; 95% CI 1.1-2.4, respectively). In men, physical activity attenuated the effect of the MC4R rs17782313 on obesity. The LEP GG genotype was associated with higher BMI, waist circumference, and visceral fat level only in men. No associations of the LEPR rs1137101 polymorphisms with anthropometric measurements and leptin level were found. In conclusion, the associations of the MC4R and LEP gene polymorphisms with obesity-related parameters strengthened with age.