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
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
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
Acute type B aortic dissection (ABAD) is a life-threatening cardiovascular disease. A practicable and effective prediction model to predict and evaluate the risk of in-hospital death for ABAD is ...required. The present study aimed to construct a prediction model to predict the risk of in-hospital death in ABAD patients.
A total of 715 patients with ABAD were recruited in the first affiliated hospital of Xinjiang medical university from April 2012 to May 2021. The information on the demographic and clinical characteristics of all subjects was collected. The logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and nomogram were applied to screen the appropriate predictors and to establish a prediction model for the risk of in-hospital mortality in ABAD. The receiver operator characteristic curve and calibration plot were applied to validate the performance of the prediction model.
Of 53 (7.41%) subjects occurred in-hospital death in 715 ABAD patients. The variables including diastolic blood pressure (DBP), platelets, heart rate, neutrophil-lymphocyte ratio, D-dimer, C-reactive protein (CRP), white blood cell (WBC), hemoglobin, lactate dehydrogenase (LDH), procalcitonin, and left ventricular ejection fraction (LVEF) were shown a significant difference between the in-hospital death group and the in-hospital survival group (all P < 0.05). Furthermore, all these factors which existed differences, except CRP, were associated with in-hospital deaths in ABAD patients (all P < 0.05). Then, parameters containing LVEF, WBC, hemoglobin, LDH, and procalcitonin were identified as independent risk factors for in-hospital deaths in ABAD patients by adjusting compound variables (all P < 0.05). In addition, these independent factors were qualified as predictors to build a prediction model (AUC > 0.5, P < 0.05). The prediction model was shown a favorable discriminative ability (C index = 0.745) and demonstrated good consistency.
The novel prediction model combined with WBC, hemoglobin, LDH, procalcitonin, and LVEF, was a practicable and valuable tool to predict in-hospital deaths in ABAD patients.
The present study was aimed to establish a prediction model for in-stent restenosis (ISR) in subjects who had undergone percutaneous coronary intervention (PCI) with drug-eluting stents (DESs).
A ...retrospective cohort study was conducted. From September 2010 to September 2013, we included 968 subjects who had received coronary follow-up angiography after primary PCI. The logistic regression analysis, receiver operator characteristic (ROC) analysis, nomogram analysis, Hosmer-Lemeshow χ
statistic, and calibration curve were applied to build and evaluate the prediction model.
Fifty-six patients (5.79%) occurred ISR. The platelet distribution width (PDW), total cholesterol (TC), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and lesion vessels had significant differences between ISR and non-ISR groups (all P < 0.05). And these variables were independently associated with ISR (all P < 0.05). Furthermore, they were identified as predictors (all AUC > 0.5 and P < 0.05) to establish a prediction model. The prediction model showed a good value of area under curve (AUC) (95%CI): 0.72 (0.64-0.80), and its optimized cut-off was 6.39 with 71% sensitivity and 65% specificity to predict ISR.
The incidence of ISR is 5.79% in CAD patients with DES implantation in the Xinjiang population, China. The prediction model based on PDW, SBP, TC, LDL-C, and lesion vessels was an effective model to predict ISR in CAD patients with DESs implantation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Little is known about isolated diastolic hypertension (IDH) among different ethnicity groups. We aimed to investigate the prevalence and risk factors for IDH among the major ethnicity population i.e. ...Han, Uygur and Kazakh in Xinjiang, northwestern part of China.
In total, 14,618 adult participants (7,799 males, 6,819 females) were recruited from the Cardiovascular Risk Survey conducted during 2007 and 2010. Blood pressure, body mass index and standard lipid profile and fasting glucose level from plasma were measured.
The overall prevalence of IDH was 10.8% in the Han, 4.5% in the Uygur and 8.7% in the Kazakh populations. When stratified by gender, IDH prevalence was 9.8% in men and 6.8% in women (P<0.001). The prevalence of IDH also varied significantly with age and it was highest in those aged 35-44 yrs old (9.7%) and lowest in those over 75 yrs old (4.1%, P<0.001). Multivariate logistic regression analysis showed that overweight (OR = 1.179, 95%CI: 1.015-1.369) or obesity (OR = 1.202, 95%CI: 1.015-1.424), smoking (OR = 1.362, 95%CI: 1.156-1.604) and high total cholesterol (TC) hyperlipidemia (OR = 1.237, 95%CI: 1.074-1.423) were significantly associated with a higher prevalence of IDH. Identified risk factors for IDH differed among ethnicity groups with male gender, young age (35-44 yrs old), more coffee or tea consumption and high TC hyperlipidemia in the Han; smoking and often coffee or tea consumption in the Uygur and male gender and overweight or obesity in the Kazakh populations.
IDH prevalence in the Han population is higher than that in the Uygur and Kazak populations in Xinjiang, northwestern part of China. Male gender, middle age, overweight or obesity, smoking and high TC hyperlipidemia appear to be relevant risk factors of IDH in adults. Different ethnicity background had different sets of risk factors for IDH.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. ...Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (H
O
) by inhibiting the NF-κB pathway.
The IκBα
gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to H
O
treatment. NRVMs were divided into control, H
O
, GFP + H
O
, IκBα+H
O
, and pyrrolidine dithiocarbamate (PDTC) + H
O
groups. Nuclear translocation of the NF-κB p65 subunit was evaluated by immunofluorescence and Western blotting. Cell viability was assessed by Cell Counting Kit-8 assay. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H
O
-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD staining, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Western blotting was used to detect apoptosis- and autophagy-related proteins.
IκBα transfection significantly increased cell viability and ΔΨm but decreased the supernatant LDH and cellular MDA levels in cardiomyocytes exposed to H
O
. Meanwhile, IκBα overexpression decreased H
O
-induced apoptosis by upregulating the Bcl-2/Bax ratio and reduced autophagy by downregulating the expression of Beclin-1 and the LC3-II/LC3-I ratio. These effects partly accounted for the ability of IκBα to inhibit the NF-κB signalling pathway, as evidenced by decreases in p65 phosphorylation and nuclear translocation. Indeed, the effects of inactivation of NF-κB signalling with the specific inhibitor PDTC resembled the cardioprotective effects of IκBα during H
O
stimulation.
IκBα overexpression can ameliorate H
O
-induced apoptosis, autophagy, oxidative injury, and ΔΨm loss through inhibition of the NF-κB signalling pathway. These findings suggest that IκBα transfection can result in successful resistance to oxidative stress-induced damage by inhibiting NF-κB activation, which may provide a potential therapeutic target for the prevention of myocardial I/R injury.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute aortic dissection (AAD) is a serious life-threatening cardiovascular condition. It is necessary to find rapid and accurate biomarkers for the diagnosis of AAD. This study aimed to determine the ...efficacy of serum amyloid A1 (SAA1) in the diagnosis and prediction of long-term adverse events in AAD.
Four-dimensional label-free quantification (4D-LFQ) technique was used to identify the differentially expressed proteins (DEPs) in aortic tissues of AAD. After comprehensive analysis, SAA1 was identified as a potential biomarker of AAD. ELISA was used to confirm the expression of SAA1 in serum of AAD patients. Moreover, the source of SAA1 in serum was explored by constructing AAD mouse model.
A total of 247 DEPs were identified, of which 139 were upregulated while 108 were downregulated. SAA1 was nearly 6.4-fold and 4.5-fold upregulated in AAD tissue and serum. ROC curve and Kaplan-Meier survival curve confirmed the good efficacy of SAA1 for the diagnosis and prediction of long-term adverse events in AAD. In vivo experiments revealed that SAA1 was mainly derived from the liver when AAD occurred.
SAA1 can be used as a potential biomarker for AAD with effective diagnostic and prognostic value.
Despite the advances in medical technology in recent years, the mortality rate of acute aortic dissection (AAD) is still high. It is still challenging for clinicians to diagnose AAD patients on time and reduce the mortality rate. In this study, 4D-LFQ technology was used to identify serum amyloid A1 (SAA1) as a potential biomarker of AAD and was verified in subsequent work. The results of this study determined the efficacy of SAA1 in the diagnosis and prediction of long-term adverse events in patients with AAD.
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•Five potential biomarkers of acute aortic dissection (AAD) were screened out by the 4D-LFQ proteomics method.•SAA1 was highly expressed both in the aortic tissues and circulation of AAD patients.•SAA1 was identified as a novel biomarker for the prediction of long-term mortality of AAD.•Elevated circulating SAA1 after AAD was mainly produced by liver.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Following myocardial ischemic injury, the most effective clinical intervention is timely restoration of blood perfusion to ischemic but viable myocardium to reduce irreversible myocardial necrosis, ...limit infarct size, and prevent cardiac insufficiency. However, reperfusion itself may exacerbate cell death and myocardial injury, a process commonly referred to as ischemia/reperfusion (I/R) injury, which primarily involves cardiomyocytes and cardiac microvascular endothelial cells (CMECs) and is characterized by myocardial stunning, microvascular damage (MVD), reperfusion arrhythmia, and lethal reperfusion injury. MVD caused by I/R has been a neglected problem compared to myocardial injury. Clinically, the incidence of microvascular angina and/or no-reflow due to ineffective coronary perfusion accounts for 5–50% in patients after acute revascularization. MVD limiting drug diffusion into injured myocardium, is strongly associated with the development of heart failure. CMECs account for > 60% of the cardiac cellular components, and their role in myocardial I/R injury cannot be ignored. There are many studies on microvascular obstruction, but few studies on microvascular leakage, which may be mainly due to the lack of corresponding detection methods. In this review, we summarize the clinical manifestations, related mechanisms of MVD during myocardial I/R, laboratory and clinical examination means, as well as the research progress on potential therapies for MVD in recent years. Better understanding the characteristics and risk factors of MVD in patients after hemodynamic reconstruction is of great significance for managing MVD, preventing heart failure and improving patient prognosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Oxidative stress injury is one of the main mechanisms of ischemia-reperfusion (I/R) injury. The extracellular signal-regulated kinase (ERK1/2) pathway plays an important role in cardioprotective ...during acute myocardial infarction. In this study, we used constitutively active MEK1 gene (CaMEK) transfection strategy to investigate whether CaMEK provides a protective effect against apoptosis and autophagy induced by Hydrogen peroxide (H
O
) in neonatal rat cardiac ventricular cardiomyocytes (NCMs) and the underlying mechanisms. As a result, CaMEK attenuated H
O
-induced apoptosis and cytotoxicity in NCMs, evidenced by decreased apoptotic cells and the ratio of Bax/Bcl-2, increased the mitochondrial membrane potential (Δψm) and cell vitality and reduced the level of lactate dehydrogenase (LDH). Further studies revealed that CaMEK attenuated H
O
-induced autophagy, evidenced by the decreased LC3-Ⅱ/LC3-Ⅰratio and SQSTM1/p62 (p62) degradation. Furthermore, we demonstrated that CaMEK phosphorylated the ERK1/2 pathway-related proteins, ERK1/2, p70S6K and GSK3β, in NCMs with H
O
stimulation. In contrast, these effects could be reversed by co-treatment with the ERK1/2 inhibitor, PD98059. These results suggest that CaMEK plays an important role in protecting cardiomyocytes against H
O
-induced injury and autophagy in NCMs via ERK1/2 pathway. Therefore, transfection of CaMEK may provide a hopeful therapeutic strategy for I/R.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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