[The Effect of Interference of NLRP3 with shRNA on AGEs-induced Inflammatory Response in Myocardial Cell].

OBJECTIVE: This study aims to explore the effect of silence of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome on advanced glycation end products (AGEs)-induced myocardial injury. METHODS: The myocardial injury model was indued by AGEs. NLRP3 was silenced by shRNA. H9c2 cells were divided into four groups: H9c2 (control group); AGEs group; AGEs+sh-Ctrl group; AGEs+sh-NLRP3 group. The latter two groups of cells will first shRNA control (sh-Ctrl) and shRNA-NLRP3 (sh-NLRP3) plasmids were transfected into H9c2 cells, the last 3 cells were then treated for 24 h with 100 mg/L AGEs, establishment of H9c2 damage model, control cells were treated with solvent for 24 h; Apoptosis was measured by Hoechst33258 staining. The levels of interleukin (IL)-6, IL-18 and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). The protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-3, Caspase-9, nuclear factor κB (NF-κB) P65 and p-P65 were tested by Western blot. The nuclear NF-κB P65 levels were detected by immunofluorescent staining. RESULTS: The expressions of NLRP3, ASC, Caspase-3 and Caspase-9 in AGEs group and AGEs+sh-Ctrl group was higher than control group ( P<0.05). Compared with AGEs group, the expressions of NLRP3, ASC, Caspase-3 and Caspase-9 in AGEs+sh-NLRP3 group was decreased ( P<0.05). Compared with control group, the apoptosis and the levels of IL-6, IL-18 and IL-1ß in AGEs group and AGEs+sh-Ctrl group were elevated ( P<0.05). The apoptosis and the levels of IL-6, IL-18 and IL-1ß in AGEs+sh-NLRP3 group were lower than those of AGEs group ( P<0.05). The phosphorylation of NF-κB P65 and nuclear NF-κB P65 in AGEs group and AGEs+sh-Ctrl group were higher than control group ( P<0.05). Compared with AGEs group, the phosphorylation of NF-κB P65 and nuclear NF-κB P65 in AGEs+sh-NLRP3 group were reduced ( P<0.05). Conlusion Silencing of NLRP3 inflammasome alleviates AGEs-induced apoptosis and inflammatory response in myocardial cell via inhibiting NF-κB P65 activation.

Association between epicardial adipose tissue and adverse outcomes in coronary heart disease patients with percutaneous coronary intervention.

We assessed the relationship between the volume of epicardial adipose tissue and long-term outcomes in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). The patients with CHD were followed for at least 2 years after PCI. The epicardial adipose tissue volume (EATV) was measured using multi-slice computed tomography. Cox regression analysis was used to examine the relationship between EATV and clinical outcome. In this study, 500 patients were enrolled and followed up for a median of 25.2 months. The incidence of adverse cardiovascular events was 12.4%. No significant differences were observed in age, sex, proportion of patients with hypertension or diabetes, smoking, drinking, total cholesterol, triglyceride, high-density lipoprotein, or unstable angina pectoris among different EATV quartiles (P>0.05). The EATV was associated with body mass index (P<0.0001), low-density lipoprotein level (P=0.039), high-sensitivity C-reactive protein level (P<0.001), uric acid level (P=0.004), adiponectin level (P<0.001), and left ventricular ejection fraction (P<0.001). Kaplan-Meier analysis indicated a significant difference in survival rate of patients in EATV quartile 1 versus 4 (P=0.019). After adjusting for confounding factors, EATV quartile 4 (>216.15 cm3) was still associated with adverse cardiovascular outcomes (HR = 1.98, 95% CI: 1.15-4.47, P=0.023) compared with quartile 1 (<101.58 cm3). Our data suggest that EATV is an independent predictor of long-term major adverse cardiovascular events in CHD patients after PCI. Therefore, assessment of EATV using multi-slice computed tomography may contribute to risk stratification in these patients.

Association between CYP3A4 gene rs4646437 polymorphism and the risk of hypertension in Chinese population: a case-control study.

Using a case-control design, we assessed the association between single nucleotide polymorphisms of CYP3A4 gene rs4646437 polymorphism and the risk of hypertension in Chinese population. We recruited 450 hypertension patients from The First Clinical College, Henan University of Chinese Medicine between June 2017 and May 2018. There was a significant difference in genotype distribution between case group and control group (χ2 =18.169, P=0.000). The minor A allele was significantly higher in the case group than that in the control group (31.0 vs 24.8%, P=0.000, odds ratio [OR]=1.36, 95% confidence interval [95% CI]: 1.12-1.66). Significant differences were also observed in other gene models: the GA/AA genotype did not increase the risk of hypertension compared with GG genotype (OR=1.16, 95% CI: 0.90-1.49, P=0.259). Compared with GG/GA genotype, the AA genotype also increased the risk of hypertension (OR=2.34, 95% CI: 1.56-3.50, P=0.000). For additive model, the AA genotype was significantly associated with GG genotype (OR=2.25, 95% CI: 1.49-3.42, P=0.000). The same results were found for AA vs GA (OR=2.50, 95% CI: 1.60-3.89, P=0.000). For the allele genotype, the A allele frequency was significantly higher in the case group than that in the control group (31.0 vs 24.8%, P=0.002). The A allele of CYP3A4 rs4646437 was associated with an increased risk for hypertension (OR=1.36, 95% CI: 1.12-1.66, P=0.002). Our results revealed a possible genetic association between CYP3A4 gene rs4646437 and hypertension, and the AA genotype of rs4646437 increased the risk of hypertension in Chinese Han population, and this effect could be confirmed by multivariable analyses.

Interaction between GDF5 gene polymorphisms and environment factors increased the risk of knee osteoarthritis: a case-control study.

Using a case-control design, we assessed the association between single nucleotide polymorphisms (SNPs) of growth and differentiation factor 5 (GDF5)/rs143383 gene and interaction with environments and knee osteoarthritis (KOA). We recruited 288 KOA patients from the First Clinical College, Henan University of Chinese Medicine between June 2017 and May 2018. There was significant difference in genotype distribution between case group and control group (χ2 = 22.661, P=0.000). The minor C allele was significantly higher in the case group than that in the control group (20.5 vs 8.1%, P=0.000, odds ratio (OR) = 1.62, 95% confidence interval (CI): 1.29-2.03). Significant differences were also observed in other gene models. For age, all models show significant differences (P<0.05) for those whose age was more than 60 years, and no significant difference was observed for those under 60 years. For non-smoking group, there were significant differences between case group and control group, and for smoker, significance level was found in TT compared with CC and allele gene models. Patients with drinking and Bbody mass index (MI )≥ 24 also showed significant relationship between rs143383 and osteoarthritis (OA) under the following models: TT vs CC (P=0.000, P=0.018), TT/CT vs CC (P=0.043), TT vs CT/CC (P=0.000, P=0.009), and T vs C (P=0.024, P=0.000). Other gene models indicated no significance (P>0.05). Our results revealed a possible genetic association between GDF5 and KOA, and the TT genotype of rs143383 increased the risk of KOA in Chinese Han population. The interaction between GDF5 gene and drinking, smoking, and obesity further increased the risk of KOA.

The rs3850641 polymorphism of the TNFSF4 gene increases the risk of myocardial infarction in a Chinese Han population.

Tumor necrosis factor superfamily member 4 (TNFSF4), also known as Ox40 ligand (Ox40l), plays an important role in atherosclerosis development. Several studies reported the association between the rs3850641 polymorphism of the TNFSF4 gene and the risk of myocardial infarction (MI). However, the results are inconsistent. In order to explore the relationship between the rs3850641 polymorphism of the TNFSF4 gene and MI, we conducted a case-control study including 454 cases and 512 controls in a Chinese Han population. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The present study found that AA genotype (AA vs. GG: odds ratio (OR) & 95% confidence interval (CI), 2.00(1.04,3.86), P=0.039; AA vs. AG+GG: OR & 95% CI, 1.93(1.00,3.70), P=0.049) or A allele carriers (A vs. G: OR & 95% CI, 1.27(1.00,1.60), P=0.047) of the rs3850641 polymorphism of the TNFSF4 gene increased the risk of MI. In conclusion, this case-control study confirms that the rs3850641 polymorphism of the TNFSF4 gene increases the risk of MI.

High-dose atorvastatin reduces the risk of cardiovascular events in patients with percutaneous coronary intervention.

We systematically searched in PubMed, Web of Science, Embase and China National Knowledge Infrastructure from the inception to March 31, 2017, identified relevant trials about efficacy of high-does Atorvastatin for patients with percutaneous coronary intervention. Twelve studies with the number of 2801 patients were included in the meta-analysis. Compared with control group, high-does Atorvastatin significantly reduced the risk of myocardial infarction in patients with percutaneous coronary intervention (Relative risk =0.62, 95% confidence interval: 0.49-0.78), with low level of heterogeneity (I2=22.6%, P=0.228). Nine studies with 2248 patients reported the adverse cardiovascular events. A fixed-effect model was applied. Compared with control group, patients with high-does Atorvastatin taken, the risk of adverse cardiovascular events was degraded by 65% (Relative risk, RR=0.65, 95% confidence interval (CI): 0.50-0.84), which was confirmed by trial sequential analysis as the cumulative Z curve entered the futility area. The subgroup analyses found that decreased risks of myocardial infarction among trails (RR=0.64, 95%CI: 0.50-0.83, RR=0.55, 95%CI: 0.34-0.88). Egger and Begg's test found no publication bias (t=-1.670, P=0.129; Z=1.560, P=0.119). The use of high-dose Atorvastatin could reduce the risk of myocardial infraction and cardiovascular adverse events in patients with percutaneous coronary intervention. High-dose Atorvastatin was recommended as an adjunct to aid percutaneous coronary intervention.

Intracoronary administration of tirofiban during percutaneous coronary intervention facilitates patients with acute coronary syndrome.

We assessed the efficacy and safety of tirofiban intracoronary versus intravenous administration during percutaneous coronary intervention for patients with acute coronary syndrome. The databases of PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang Database were retrieved. A total of 437 articles were found, according to inclusive and exclusive criteria, 13 of which were finally included. Compared with subjects with intravenous administration, those with intracoronary administration were more likely to reach thrombolysis in myocardial infarction trial grade 3 flow (relative risk = 1.17, 95% confidence interval: 1.11-1.22), improve left ventricular ejection fraction (Standardized mean difference = 0.65, 95% confidence interval: 0.20-1.11). Intracoronary administration resulted in a reduced risk of major adverse cardiovascular events at 30-day follow-up (relative risk = 0.47, 95% confidence interval: 0.34-0.65). However, incidence of bleeding complications was not statistically significant between two groups (relative risk = 0.76, 95% confidence interval: 0.55-1.04). Intracoronary administration of tirofiban can be more effective in increasing coronary blood flow and microvascular perfusion, more effective in improving postoperative myocardial reperfusion, more significantly in reducing the incidence of adverse cardiovascular events at 30-day's follow-up and improving the prognosis after percutaneous coronary intervention without increasing the risk of bleeding.

Helicobacter pylori infection and pepsinogen levels have clinical significance in hypertension patients.

Helicobacter pylori (Hp) infection is known to alter levels of pepsinogens (PG) and is correlated with several disease states, including gastric and cardiovascular diseases. This study sought to assess whether Hp infection is associated with hypertension as well as to identify the value of assessing the PG I/PG II ratio in patients with hypertension. The study included 396 individuals with hypertension who were assessed for infection with Hp by colloidal gold assay. Participants' weight, height, blood pressure, and serum lipids were measured, and participants were examined for the presence of renal or ocular damage. H. pylori infection status or PG I/PG II ratio were compared against other variables (e.g., body mass index, serum cholesterol, diastolic blood pressure) by t-test or ⇨(2) test, and Pearson's correlation analysis was used to identify associations. Consistent with other studies, the PG I/PG II ratio of patients with Hp infection was significantly lower than that of patients without Hp infection (P < 0.001). The serum total cholesterol and triglycerides of patients with Hp infection were significantly higher than those of patients without Hp infection (P < 0.001), and the PG I/PG II ratio was negatively correlated with total cholesterol (r=-0.61) and triglycerides (r=-0.56) levels. However, there was no significant difference in hypertension severity by Hp infection status or PG I/PG II ratio. Interestingly, the PG I/PG II ratio was significantly lower in patients with hypertensive nephropathy or hypertensive retinopathy than in patients without these symptoms (P < 0.05). The areas under the receiver-operating characteristic curve were 0.77 and 0.83 in the diagnosis of nephropathy and retinopathy, respectively. These findings indicate that the PG I/PG II ratio is lower in individuals with hypertensive nephropathy and hypertensive retinopathy. Thus, the detection of the PG I/PG II ratio may be valuable for diagnostic screening for hypertensive organ damage.