Effects of Trimetazidine on Ventricular Remodeling and Serum Levels of Cys C and ET-1 in Patients with CHF.

Objective: To analyze the effects of trimetazidine on ventricular remodeling and serum cystatin C (Cys C) and endothelin-1 (ET-1) levels in patients with chronic heart failure (CHF). Methods: A total of 96 patients with CHF admitted to the fifth affiliated hospital of Xinjiang medical university. were enrolled as the research objects between June 2012 and June 2023. They were randomly divided into a control and observation groups, with 48 cases in each group. The control group was given routine treatment, while the observation group was additionally treated with trimetazidine hydrochloride tablets. All were continuously treated for 6 months. The clinical curative effect between the two groups was compared. The left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) were measured by cardiac echocardiography before and after treatment. 6MVT before and after treatment was recorded. A full-automatic biochemical analyzer detected the level of serum Cys C before and after treatment. The levels of serum ET-1, galectin-3 (Gal-3), brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) were detected by enzyme-linked immunosorbent assay before and after treatment. The incidence of adverse events in the two groups of CHF patients was compared. Results: The total response rate of treatment in the observation group was significantly higher than that in the control group (91.67% vs 79.17%) (P = .037). After treatment, LVEDD and LVESD decreased, while LVEF and 6MVT increased in both groups. LVEDD and LVESD in the observation group were significantly lower than those in the control group, while LVEF and 6MVT were significantly higher than those in the control group (P < .05). After treatment, serum Cys C, ET-1, Gal-3, BNP, and ANP levels in both groups were significantly decreased, significantly lower in the observation group than in the control group (P < .05). The readmission rate of the observation group was lower than that of the control group (P = .045). There was no significant difference in mortality between the two groups (P = .315). Conclusion: Trimetazidine is effective in treating patients with CHF. It can improve cardiac function and reduce the rate of re-hospitalization.

Differential gene expression and miRNA regulatory network in coronary slow flow.

Coronary slow flow (CSF) is characterized by slow progression of coronary angiography without epicardial stenosis. The aim of this study was to explore the potential biomarkers and regulatory mechanism for CSF. Peripheral blood mononuclear cells from 3 cases of CSF and 3 healthy controls were collected for high-throughput sequencing of mRNA and miRNA, respectively. The differentially expressed mRNAs (DE-mRNAs) and miRNAs (DE-miRNAs) was identified. A total of 117 DE-mRNAs and 32 DE-miRNAs were obtained and they were mainly enriched in immune and inflammatory responses. Twenty-six DE-mRNAs were the predicted target genes for miRNAs by RAID, and then the regulatory network of 15 miRNAs were constructed. In addition, through the PPI network, we identified the three genes (FPR1, FPR2 and CXCR4) with larger degrees as hub genes. Among them, FPR1 was regulated by hsa-miR-342-3p, hsa-let-7c-5p and hsa-miR-197-3p and participated in the immune response. Finally, we validated the differential expression of hub genes and key miRNAs between 20 CSF and 20 control. Moreover, we found that miR-342-3p has a targeted regulatory relationship with FPR1, and their expression is negatively correlated. Then we established a hypoxia/reoxygenation (H/R) HUVEC model and detected FPR1, cell proliferation and apoptosis. Transfection with miR-342-3p mimics can significantly promote the proliferation of HUVEC under H/R conditions. FPR1 were associated with CSF as a biomarker and may be regulated by miR-342-3p potential biomarkers.

The Tp-e/QT ratio as a predictor of nocturnal premature ventricular contraction events in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is significantly associated with a higher risk of ventricular arrhythmia (VA). QT, the Tp-e/QT ratio, and QT dispersion (QTd) are used to evaluate myocardial repolarization and are highly correlated with VA. The aim was to evaluate the predictive value of the Tp-e/QT ratio and other electrocardiogram (ECG) parameters for nocturnal premature ventricular contractions (PVCs) in patients with OSA. METHODS: We retrospectively analyzed data from patients with OSA and conducted a 1:1 matched cohort study. Patients diagnosed with OSA who met our criteria for the PVC group, and sex- and age-matched patients with OSA who met our criteria for the control group were enrolled in the study. The Tp-e, Tp-e/QT ratio, corrected QT interval (QTc), corrected Tp-e interval (Tp-ec), and QTd were measured, calculated and analyzed. RESULTS: Patients in the PVC group (n = 31) showed a greater Tp-e, Tp-ec, QTc, Tp-e/QT ratio, and QTd than patients in the control group (n = 31). In the univariate binary logistic regression analysis, higher Tp-ec (OR: 1.025; P = 0.042), QTc (OR: 1.014; P = 0.036), Tp-e/QT ratio (OR: 1.675; P < 0.001), and QTd (OR: 1.052; P = 0.012) values were all significantly associated with nocturnal PVCs. In multivariate analysis and receiver operating characteristic analysis, a higher Tp-e/QT ratio (OR: 2.168; 95% CI: 0.762-0.952; P < 0.001) was an independent predictor of nocturnal PVCs. CONCLUSIONS: The QTc, Tp-e/QT ratio, and QTd in patients with OSA with nocturnal PVCs were significantly increased compared with those in patients without nocturnal PVCs. A prolonged Tp-e/QT ratio was an independent predictor of nocturnal PVCs in patients with OSA.

NLRC5 enhances autophagy via inactivation of AKT/mTOR pathway and ameliorates cardiac hypertrophy.

The aim of this study was to investigate the effect of nucleotide-binding oligomerization domain (NOD)-like receptor family CARD domain containing 5 (NLRC5) in cardiac hypertrophy, and to explore the mechanism implicated in this effect Cardiac hypertrophy was induced in neonatal rat cardiac myocytes using 1 µM of angiotensin II (Ang II) for 12, 24 and 48 h. Overexpression of NLRC5 was induced in H9C2 cells, and the NLRC5 + Ang II-treated cells were exposed to SC9 and 3-methyladenine (3MA). An immunofluorescence assay was used for α-actinin staining, and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for NLRC5, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) determination. Western blot analysis was applied to measure the levels of NLRC5, microtubule-associated protein 1A/1B-light chain 3 type I (LC3I), LC3II, sequestosome 1 (p62), protein kinase B (AKT), phosphorylated Akt (pAKT), mammalian target of rapamycin (mTOR) and phosphorylated mTOR (pmTOR). The level of NLRC5 was significantly decreased after Ang II treatment in cardiomyocytes, but the levels of ANP and BNP were increased. Overexpression of NLRC5 reduced the cell size, downregulated the levels of ANP and BNP, increased LC3II / LC3I, but decreased p62 in Ang II-induced cardiomyocyte hypertrophy. In addition, the results from Western blot showed that overexpression of NLRC5 distinctly decreased the ratios of pAKT/AKT and pmTOR/mTOR in cardiomyocyte hypertrophy. SC79 and 3MA significantly downregulated the ratio of LC3I/LC3II but increased the level of p62 in NLRC5 + Ang II-treated cells. These results provide a possible novel therapeutic strategy for cardiac hypertrophy that might be useful in a clinical setting.

Atrial fibrillation in obstructive sleep apnea: Neural mechanisms and emerging therapies.

Obstructive sleep apnea (OSA) has been reproducibly identified as a risk factor for initiation and progression of atrial fibrillation (AF) and reduces the efficacy of antiarrhythmic drugs, electrical cardioversion, and catheter ablation in AF. It is still controversial whether continuous positive airway pressure ventilation (CPAP) could improve the successful rate of AF treatment in OSA patients. Besides, CPAP has shown relative low compliance in patients with OSA. Therefore, novel optional therapies might be needed to improve the control of AF associated with OSA. A growing body of evidence suggests that autonomic activation contributes to the pathogenesis of AF in OSA. Acute apneic episodes result in sympathovagal co-activation, shortening atrial refractoriness and promoting the initiation of AF. Chronic OSA-induced sympathetic activation plays a crucial role in atrial autonomic, structural, and electrical remodeling, thus providing substrates for AF maintenance and recurrence. Therefore, the autonomic nervous system may be a promising therapeutic target for OSA and AF. Autonomic modulation as a treatment for OSA-associated AF has been well established in several preclinical studies. Further clinical studies are needed to provide a more precise definition of the role of autonomic modulation in the treatment of AF in OSA.

Atorvastatin improves the proliferation and migration of endothelial progenitor cells via the miR-221/VEGFA axis.

The present study was aimed at investigating the detailed functions of atorvastatin, a lipid-lowering agent, in the pathogenesis of coronary slow flow (CSF), a clinical disease characterized by delayed angiographic coronary opacity without obstructive coronary disease. In the present study, we successfully identified isolated endothelial progenitor cells (EPCs) from the peripheral blood of patients with CSF. Their vascular endothelial growth factor-A (VEGFA) protein levels were determined using immunoblotting analyses. We determined cell viability using MTT assays, cell migration capacity using Transwell assays, and the angiogenic capacity using a tube formation assay. The target association between miR-221 and VEGFA was validated with a luciferase reporter assay. Atorvastatin treatment increased EPC VEGFA protein levels, proliferation, migration, and angiogenesis. miR-221 expression was down-regulated after atorvastatin treatment; miR-221 overexpression exerted an opposing effect to atorvastatin treatment on VEGFA protein, EPC proliferation, migration, and angiogenesis. The protective effects of atorvastatin treatment on VEGFA protein and EPCs could be significantly suppressed by miR-221 overexpression. miR-221 directly bound the VEGFA 3'UTR to inhibit its expression. In conclusion, atorvastatin improves the cell proliferation, migration, and angiogenesis of EPCs via the miR-221/VEGFA axis. Thus, atorvastatin could be a potent agent against CSF, pending further in vivo and clinical investigations.

[Association of the neprilysin and apolipoprotein E gene polymorphisms with Alzheimer's disease in Xinjiang Uygur population].

OBJECTIVE: To assess the association between the neprilysin (NEP) gene and apolipoprotein E (ApoE) gene polymorphisms and sporadic Alzheimer's disease (SAD) in Xinjiang Uygur population. METHODS: The polymorphisms of the NEP and ApoE gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 111 SAD patients and 117 healthy controls. RESULTS: (1) The frequency of the T allele in the NEP gene was significantly higher in the SAD patients than that in the controls (Chi-square= 5.005, P< 0.05); and there was higher risk to develop SAD in the T allele carriers. (2) The frequency of the ApoE 4 epsilon 4 allele was higher in the SAD patients than in the controls (Chi-square= 4.218, P< 0.05); and the ApoE 4 epsilon 4 carriers had significantly increased risk of developing SAD. (3) No significant interaction was found between the NEP and ApoE polymorphisms in SAD patients. CONCLUSION: The NEP and ApoE gene polymorphisms may be associated with SAD. NEP gene may be an independent genetic risk factor for SAD in Xinjiang Uygur population.