Abstract
PCSK9 plays a crucial role in lipid metabolism. This case–control study explored the associations of novel single nucleotide polymorphisms (SNPs) of the PCSK9 gene with coronary artery ...disease (CAD) (≥ 1 coronary artery stenosis ≥ 50%) and its risk factors in the Han population in Xinjiang, China. Four tag SNPs (rs11583680, rs2483205, rs2495477 and rs562556) of the PCSK9 gene were genotyped in 950 CAD patients and 1082 healthy controls. The distributions of genotypes in rs2483205 and rs562556 were significantly different between the groups (all
p
< 0.05). The TT genotype of rs2483205, GG genotype of rs562556, and their H4 (T-G) haplotype were associated with CAD odds ratio (OR) 0.65, confidence interval (CI) 0.45–0.95, p = 0.024; 0.63, 0.45–0.90, p = 0.011; 0.50, 0.35–0.70, p < 0.001, respectively. Additionally, the model (TT + CT vs. CC) of rs2483205 was associated with increased risk of obesity, and the G allele of rs562556 was associated with lower low-density lipoprotein cholesterol (LDL-C), blood glucose, body mass index (BMI), and mean platelet volume (MPV) (all p < 0.05). rs2483205, rs562556, and their H4 haplotype of the PCSK9 gene were associated with CAD. Additionally, rs2483205 is associated with obesity, and rs562556 is associated with LDL-C, blood glucose, BMI, and MPV.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Dyslipidemia is one of the main risk factors for coronary heart disease (CHD). The E3 ubiquitin ligase which is encoded by the ring finger protein 145 (RNF145) gene is very important in the mediation ...of cholesterol synthesis and effectively treats hypercholesterolemia. Thus, the purpose of the present research is to investigate the connection between the polymorphism of the RNF145 gene and cholesterol levels in the populations in Xinjiang, China. A total of 1396 participants (Male: 628, Female: 768) were included in this study for genetic analysis of RNF145 gene, and we used the modified multiple connection detection response (iMLDR) technology to label two SNPs (rs17056583, rs12188266) of RNF145 genotyping. The relationship between the genotypes and the lipid profiles was analyzed with general linear model analysis after adjusting confounding variables. Through the analysis of the two SNPs in RNF145 gene, we discovered that both rs17056583 and rs12188266 were related to total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations (All P < 0.001). In addition, the association of rs17056583 and rs12188266 with lipid profiles concentrations is still statistically significant after multivariate adjustment of sex, age, smoking, obesity, drinking, diabetes, hypertension and lipid profiles. Meanwhile, we also found that rs17056583 was associated with high triglycerides concentrations before and after adjustment (All P < 0.001). Our study shows that both rs17056583 and rs12188266 SNPs of RNP145 gene are related to TC and LDL-C concentrations in Xinjiang population.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in ...pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH.
Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators.
Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hyperlipidemia is one of the main risk factors that contributed to atherosclerosis and coronary artery disease (CAD). In the present study, our objective was to explore whether some genetic variants ...of human IDOL gene were associated with hyperlipidemia among Han population in Xinjiang, China. We designed a case-control study. A total of 1,172 subjects (588 diagnosed hyperlipidemia cases and 584 healthy controls) of Chinese Han were recruited. We genotyped three SNPs (rs9370867, rs909562, and rs2072783) of IDOL gene in all subjects by using the improved multiplex ligation detection reaction (iMLDR) method. Our study demonstrated that the distribution of the genotypes, the dominant model (AA vs GG + GA), and the overdominant model (AA + GG vs GA) of the rs9370867 SNP had significant differences between the case group and controls (all P < 0.001). For rs909562 and rs2072783, the distribution of the genotypes, the recessive model (AA + GA vs GG) showed significant differences between the case subjects and controls (P = 0.002, P = 0.007 and P = 0.045, P = 0.02, respectively). After multivariate adjustment for several confounders, the rs9370867 SNP is still an independent risk factor for hyperlipidemia odds ratio (OR) = 1.380, 95% confidence interval (CI) = 1.201-1.586, P < 0.001. The rs9370867 of human IDOL gene was associated with hyperlipidemia in Han population.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pulmonary arterial hypertension (PAH) is a severe and progressive disease that affects the heart and lungs and a global health concern that impacts individuals and society. Studies have reported that ...some proteins related to mitochondrial metabolic functions could play an essential role in the pathogenesis of PAH, and their specific expression and biological function are still unclear. We successfully constructed a monocrotaline- (MCT-) induced PAH rat model in the present research. Then, the label-free quantification proteomic technique was used to determine mitochondrial proteins between the PAH group (n=6) and the normal group (n=6). Besides, we identified 1346 mitochondrial differentially expressed proteins (DEPs) between these two groups. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the mainly mitochondrial DEPs’ biological functions and the signal pathways. Based on the protein-protein interaction (PPI) network construction and functional enrichment, we screened 19 upregulated mitochondrial genes (Psmd1, Psmc4, Psmd13, Psmc2, etc.) and 123 downregulated mitochondrial genes (Uqcrfs1, Uqcrc1, Atp5c1, Atp5a1, Uqcrc2, etc.) in rats with PAH. Furthermore, in an independent cohort dataset and experiments with rat lung tissue using qPCR, validation results consistently showed that 6 upregulated mitochondrial genes (Psmd2, Psmc4, Psmc3, Psmc5, Psmd13, and Psmc2) and 3 downregulated mitochondrial genes (Lipe, Cat, and Prkce) were significantly differentially expressed in the lung tissue of PAH rats. Using the RNAInter database, we predict potential miRNA target hub mitochondrial genes at the transcriptome level. We also identified bortezomib and carfilzomib as the potential drugs for treatment in PAH. Finally, this study provides us with a new perspective on critical biomarkers and treatment strategies in PAH.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The aim of the present study was to estimate the impact of dehydroepiandrosterone sulfate (DHEAS) on the prognosis of patients with cardiovascular disease by performing a systematic review and ...meta-analysis.
The Embase, PubMed, Web of Science, CNKI, and WanFang databases were searched up to September 5, 2016, to identify eligible studies. The quality of each study was assessed using the Newcastle-Ottawa Scale. The association between DHEAS, either on admission or at discharge, and cardiovascular disease outcomes were reviewed. The overall risk ratio for the effect of DHEAS on all-cause mortality and fatal and nonfatal cardiovascular events was pooled using a fixed-effects or a random-effects model. The publication bias was evaluated using funnel plots. Twenty-five studies were included for systematic review. The follow-up duration ranged from 1 to 19 years. Eighteen studies were included in the meta-analysis. We found that lower DHEAS levels indicated a significant increased risk for all-cause mortality (risk ratio, 1.47; 95% CI, 1.38-1.56
<0.00001), fatal cardiovascular event (risk ratio, 1.58; 95% CI, 1.30-1.91
<0.00001), and nonfatal cardiovascular event (risk ratio, 1.42; 95% CI, 1.24-1.62
<0.0001) in patients with cardiovascular disease.
Patients with cardiovascular disease who have lower DHEAS levels may have poorer prognosis than those with higher DHEAS levels.
In the present study, we aimed to evaluate the prevalence of dyslipidemia in students from different ethnic groups in Xinjiang. It is an observational, cross-sectional study. The sample of 7096 ...students aged 21-25 years was randomly selected from the clinic of Xinjiang Medical University. Baseline data, serum concentration of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fasting plasma glucose (FPG) were reported. The prevalence of changes in lipid profile according to Body mass index (BMI) in three ethnic groups was calculated. Compared with Han and Uygur students, TC, LDL-C, TG and FPG levels were lower in kazakh sutdents, while HDL-C level was lower in Uygur students. The prevalence of high TC change was higher in Uygur students, and high LDL-C change was higher in Han students. The prevalence of low HDL-C change was higher in Uygur students, and high TG change was lower in Kazakh students. The prevalence of high TC, LDL-C, TG and low HDL-C changes was observed in normal weight, overweight and obesity groups according to the nutritional status by BMI among students of each ethnic group. The present study demonstrated the prevalence of dyslipidemia in students from different ethnic groups, and enriched the limited data on the early prevention and treatment of dyslipidemia and cardiovascular diseases in Xinjiang medical students crowd.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background:
Spatial transcriptomics enables gene expression events to be pinpointed to a specific location in biological tissues. We developed a molecular approach for low-cell and high-fiber ...Stanford type A aortic dissection and preliminarily explored and visualized the heterogeneity of ascending aortic types and mapping cell-type-specific gene expression to specific anatomical domains.
Methods:
We collected aortic samples from 15 patients with Stanford type A aortic dissection and a case of ascending aorta was randomly selected followed by 10x Genomics and spatial transcriptomics sequencing. In data processing of normalization, component analysis and dimensionality reduction analysis, different algorithms were compared to establish the pipeline suitable for human aortic tissue.
Results:
We identified 19,879 genes based on the count level of gene expression at different locations and they were divided into seven groups based on gene expression trends. Major cell that the population may contain are indicated, and we can find different main distribution of different cell types, among which the tearing sites were mainly macrophages and stem cells. The gene expression of these different locations and the cell types they may contain are correlated and discussed in terms of their involvement in immunity, regulation of oxygen homeostasis, regulation of cell structure and basic function.
Conclusion:
This approach provides a spatially resolved transcriptome− and tissue-wide perspective of the adult human aorta and will allow the application of human fibrous aortic tissues without any effect on genes in different layers with low RNA expression levels. Our findings will pave the way toward both a better understanding of Stanford type A aortic dissection pathogenesis and heterogeneity and the implementation of more effective personalized therapeutic approaches.
Valvular heart diseases (VHD) is very common in clinical practice and has became the subject of growing attention in the field of cardiovascular medicine. Our aim was to assess the prevalence and ...correlates of VHD in the general population in Xinjiang, China.
Using a 4-stage stratified cluster random sampling method, a total of 14618 participants were recruited in the Cardiovascular Risk Survey (CRS) study. The participants' personal information, medical history were assessed by questionnaire. VHD was diagnosed by transthoracic echocardiography. We carried out the statistical analysis utilizing SPSS Statistics version 19.0.
In the total study group, VHD was observed in 1397 (9.65%) individuals. The prevalence rates of VHD in Han, Uygur and Kazak group are 13.51%, 2.71% and 12.29% respectively. The prevalence rates of VHD increased strikingly with age (all P < 0.001). The results of multinomial regression analysis indicated that VHD were related to age in Han group, to age smoking and hypertension in Uygur group, to age and hypertension in Kazak group.
Our research provides a unique prevalence rate of VHD in Xinjiang natural population. The result suggests that VHD are notably common in this population (9.65%) and increase with age. There exists significant difference of prevalence rate between ethnics. The main risk factors of VHD are age, hypertension and smoking. Valvular heart diseases should be regarded as a serious and growing public-health problem.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aged patients suffering from acute myocardial ischemia (AMI) exhibit an increased mortality rate and worse prognosis, and a more effective treatment is currently in need. In the present study, we ...investigated potent targets related to Wnt/β-catenin pathway deregulation for AMI injury treatment.
In the present study, AAV-Sfrp1 was transduced into the myocardium of aged mice, and an AMI model was established in these aged mice to study the effect and molecular mechanism of Sfrp1 overexpression on AMI-induced injury.
The results showed that Sfrp1 was successfully overexpressed in the myocardium of aged mice and remarkably reduced Wnt/β-catenin pathway activity in aged mice after AMI, effectively reducing the degree of myocardial fibrosis, inhibiting cardiomyocyte apoptosis, and improving cardiac function. We revealed that the exogenous introduction of Sfrp1 could be considered a promising strategy for improving post-AMI injury in aged mice by inhibiting Wnt/β-catenin pathway activity.
In conclusion, the Wnt/β-catenin pathway potentially represents a key target in AMI in aged mice. Sfrp1 might be used as a small molecule gene therapy drug to improve heart function, reduce the degree of myocardial fibrosis, inhibit cardiomyocyte apoptosis and reduce AMI injury in aged mice by inhibiting the Wnt/β-catenin pathway, thereby effectively protecting aged hearts from AMI injury.
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