Left atrial size modify the association between uric acid and atrial fibrillation in patients with coronary artery disease.

BACKGROUND AND AIMS: The potential influence of left atrial size on the relationship between uric acid and atrial fibrillation has not been fully investigated. This study aims to evaluate the interaction effect of left atrial size on the association between uric acid and atrial fibrillation in patients with coronary artery disease. METHODS AND RESULTS: This retrospective cohort study, conducted from January 2018 to October 2022, included 2004 patients undergoing Drug-Eluting Stent implantation for coronary artery disease. Utilizing logistic regression models with the product of left atrial enlargement (LAE) and uric acid, interaction effects were assessed. Among the participants, 383 had LAE, and 159 experienced atrial fibrillation. After adjusting for covariates, continuous uric acid levels were associated with an increased risk of atrial fibrillation in patients without LAE (OR:1.631, 95% CI: 1.284-2.072), but not in those with LAE (OR:1.069, 95% CI: 0.848-1.348). A significant interaction of uric acid levels was observed between groups with and without LAE (p = 0.046). Restricted cubic spline curves indicated a J-shaped relationship between uric acid and atrial fibrillation in the absence of LAE. However, the association between uric acid levels and atrial fibrillation in the LAE group remained unchanged with increasing uric acid levels. CONCLUSION: The study suggested that left atrial size modified the association between uric acid and atrial fibrillation in patients with coronary artery disease. Uric acid serves as a potential biomarker for atrial fibrillation risk, especially in individuals without LAE.

Research Progress in the Relationship Between Trimethylamine Oxide and Coronary Heart Disease.

Objective: To provide a theoretical basis for intestinal intervention in the treatment of coronary heart disease. Methods: Summarizing the mechanism of trimethylamine oxide (TMAO) inducing coronary heart disease and discussing the target of clinical intervention including TMAO generation, metabolism, and other links. The authors also clarified the potential clinical value of TMAO as a predictor of cardiovascular disease．. Results: The intestinal microbiota metabolite TMAO is closely related to the occurrence and development of coronary heart disease. TMAO can induce the development of coronary heart disease by promoting endothelial cell dysfunction, promoting foam cell formation, affecting cholesterol and bile acid metabolism, and promoting platelet activation and thrombosis. Diet, physical exercise, and other ways can reshape intestinal flora, inhibit TMAO generation, and help to prevent and cure coronary heart disease. In addition, TMAO has important clinical value in predicting risk stratification and evaluating the prognosis of coronary heart disease. Conclusion: TMAO can induce and assist in the development of coronary heart disease by promoting endothelial cell dysfunction, foam cell formation, and other mechanisms. At present, diet and physical exercise can reduce the production of TMAO to a certain extent, to prevent the occurrence and development of coronary heart disease. Furthermore, TMAO is a promising predictive marker for risk stratification and evaluating the prognosis of coronary heart disease.TMAO can not only directly induce coronary heart disease by promoting endothelial cell dysfunction, foam cell formation and other mechanisms, but also promote the occurrence and development of coronary heart disease by affecting the risk factors related to coronary heart disease (such as hypertension and diabetes). It has been confirmed that diet and physical exercise can reduce the production of TMAO to a certain extent and prevent the occurrence and development of coronary heart disease. In addition, TMAO is a valuable indicator for assessing risk stratification and prognosis of coronary heart disease.

Incorporating uric acid into the CHA2DS2-VASc score improves the prediction of new-onset atrial fibrillation in patients with acute myocardial infarction.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a common cardiac arrhythmia observed in patients with acute myocardial infarction (AMI) and is associated with worse outcomes. While uric acid has been proposed as a potential biomarker for predicting atrial fibrillation, its association with NOAF in patients with AMI and its incremental discriminative ability when added to the CHA2DS2-VASc score are not well established. METHODS: We conducted a retrospective analysis of 1000 consecutive patients with AMI without a history of atrial fibrillation between January 2018 and December 2020. Continuous electrocardiographic monitoring was performed during the patients' hospital stay to detect NOAF. We assessed the predictive ability of the different scoring models using receiver operating characteristic (ROC) curves. In addition, we employed the area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) analyses to assess the incremental discriminative ability of uric acid when added to the CHA2DS2-VASc score. RESULTS: Ninety-three patients (9.3%) developed NOAF during hospitalisation. In multivariate regression analyses, the adjusted odds ratio (OR) for NOAF was 1.439 per one standard deviation increase in uric acid level (95% confidence intervals (CI):1.182-1.753, p < 0.001). The ROC curve analysis revealed that the AUC for uric acid was 0.667 (95% CI:0.601-0.719), while the AUC for the CHA2DS2-VASc score was 0.678 (95% CI:0.623-0.734). After integrating the uric acid variable into the CHA2DS2-VASc score, the combined score yielded an improved AUC of 0.737 (95% CI:0.709-0.764, p = 0.009). Furthermore, there was a significant improvement in both IDI and NRI, indicating an incremental improvement in discriminative ability (IDI = 0.041, p < 0.001; NRI = 0.627, p < 0.001). CONCLUSION: Our study suggests that uric acid level is an independent risk factor for the development of NOAF after AMI. Furthermore, the incorporation of uric acid into the CHA2DS2-VASc score significantly improves the discriminative ability of the score in identifying patients at high risk for NOAF.

The association of APOC4 polymorphisms with premature coronary artery disease in a Chinese Han population.

BACKGROUND: Hypercholesterolemia arising from abnormal lipid metabolism is one of the critical risk factors for coronary artery disease (CAD), however the roles of genetic variants in lipid metabolism-related genes on premature CAD (≤ 60 years old) development still require further investigation. We herein genotyped four single nucleotide polymorphisms (SNPs) in lipid metabolism-related genes (rs1132899 and rs5167 in APOC4, rs1801693 and rs7765781 in LPA), aimed to shed light on the influence of these SNPs on individual susceptibility to early-onset CAD. METHODS: Genotyping of the four SNPs (rs1132899, rs5167, rs1801693 and rs7765781) was performed in 224 premature CAD cases and 297 control subjects (≤ 60 years old) using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. The association of these SNPs with premature CAD was performed with SPSS software. RESULTS: Multivariate logistic regression analysis showed that C allele (OR = 1.50, P = 0.027) and CC genotype (OR = 2.84, P = 0.022) of APOC4 rs1132899 were associated with increased premature CAD risk, while the other three SNPs had no significant effect. Further stratified analysis uncovered a more evident association with the risk of premature CAD among male subjects (C allele, OR = 1.65, and CC genotype, OR = 3.33). CONCLUSIONS: Our data provides the first evidence that APOC4 rs1132899 polymorphism was associated with an increased risk of premature CAD in Chinese subjects, and the association was more significant among male subjects.

A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression.

miRNAs are small non-coding RNAs that play an important role in numerous physiological processes. Common single nucleotide polymorphisms (SNPs) in pre-miRNAs may change their property through altering miRNAs expression and/or maturation, resulting in diverse functional consequences. To date, the role of genetic variants in pre-miRNAs on coronary artery disease (CAD) risk remains poorly understood. Here we aimed to evaluate the influence of three common SNPs in pre-miRNAs (miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, miR-499 rs3746444 T>C) on individual susceptibility to CAD in a Chinese population of 295 CAD patients and 283 controls. Genotyping was performed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. In a logistic regression analysis, we detected an association of rs2910164 in pre-miR-146a with the CAD risk; compared with the GG homozygotes, the GC heterozygotes [odds ratio (OR)=1.89, 95% confidence interval (CI)=1.06-3.36, P=0.029] and the CC homozygotes (OR=1.83, 95% CI=1.01-3.32, P=0.046) genotype were statistically significantly associated with the increased risk for CADs. As we used further genotype association models, we found a similar trend of the association in recessive model (OR=1.86, 95% CI=1.09-3.19, P=0.023). We also found that the genotypes of miR-146a rs2910164 were associated with its mature miRNA expression by analyzing 23 PBMC samples from CAD patients. Individuals carrying rs11614913 GC or CC genotypes showed 3.2-fold higher expression compared to GG genotype carriers (P<0.05). We observed no association of the other two SNPs in miR-196a2 (rs11614913) and miR-499 (rs3746444) with the CAD incidence. Our data provide the first evidence that the miR-146a rs2910164 polymorphism is associated with increased risk of CAD in Chinese Han population, which may be through influencing the expression levels of the miRNA.

The LRP6 rs2302685 polymorphism is associated with increased risk of myocardial infarction.

BACKGROUND: Abnormal lipids is one of the critical risk factors for myocardial infarction (MI), however the role of genetic variants in lipid metabolism-related genes on MI pathogenesis still requires further investigation. We herein genotyped three SNPs (LRP6 rs2302685, LDLRAP1 rs6687605, SOAT1 rs13306731) in lipid metabolism-related genes, aimed to shed light on the influence of these SNPs on individual susceptibility to MI. METHODS: Genotyping of the three SNPs (rs2302685, rs6687605 and rs13306731) was performed in 285 MI cases and 650 control subjects using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. The association of these SNPs with MI and lipid profiles was performed with SPSS software. RESULTS: Multivariate logistic regression analysis showed that C allele (OR = 1.62, P = 0.039) and the combined CT/CC genotype (OR = 1.67, P = 0.035) of LRP6 rs2302685 were associated with increased MI risk, while the other two SNPs had no significant effect. Further stratified analysis uncovered a more evident association with MI risk among younger subjects (≤60 years old). Fascinatingly, CT/CC genotype of rs2302685 conferred increased LDL-C levels compared to TT genotype (3.0 mmol/L vs 2.72 mmol/L) in younger subjects. CONCLUSIONS: Our data provides the first evidence that LRP6 rs2302685 polymorphism is associated with an increased risk of MI in Chinese subjects, and the association is more evident among younger individuals, which probably due to the elevated LDL-C levels.

Application of atomic-scale mechanistic insights into carbon-catalyzed N2O reduction for kinetic modeling construction.

To achieve the collaborative elimination of N2O and carbon of potent greenhouse pollutants from automotive mobile sources, a chemical kinetic model is developed to accurately track the heterogeneous process of carbon-catalyzed N2O reduction based on density functional theory, with experimental data used to validate the model's reliability. The influence of carbon structure, site density, and surface chemical properties on N2O catalytic reduction can be analyzed within this system. Results reveal that the free-edge site of carbon accurately describes the catalytic reduction process of N2O. Adsorption of N2O to carbon edges in O-down, N-down, or parallel orientations exhibits an exothermic process with energy barriers. The N2O with O-down reduction pathway predominates due to the limitations imposed by the unitary carbon site. As the number of active carbon atoms at carbon edges increases, the N2O reaction mode tends towards parallel and N-down pathways, resulting in a significant enhancement of N2O conversion rates and a reduction in catalytic temperatures, with the lowest achievable temperature being 300 K. Furthermore, the triplet carbon structure exhibits higher efficiency in N2O catalytic reduction compared to the singlet carbon structure, achieving a remarkable N2O conversion rate of 93.8 % within the typical temperature exhaust window of diesel engines. This study supplies a breakthrough for carbon materials as catalysts for achieving high N2O conversion rates at low cost, which is important for the collaborative catalytic elimination of N2O and carbon black pollutants.

Unique intestinal microflora and metabolic profile in different stages of hypertension reveal potential biomarkers for early diagnosis and prognosis.

Introduction. Hypertension is the most prevalent chronic disease and a major risk factor for cardiovascular and cerebrovascular diseases.Gap statement. However, there has been no substantial breakthrough in aetiology, new drug targets, and drug development of hypertension in recent 50 years.Research aim. Therefore, this study was to screen unique intestinal microbiome and serum metabolic biomarkers which can early diagnose and track the prognosis of hypertension patients in different periods, and analyse its underlying mechanisms and functions.Methods. Four groups of stool and serum samples, including healthy controls (HCs), prehypertension (PHT), hypertension (HT), and hypertension-related complications (HTC), were collected. Microbial diversity assessed using 16S rRNA sequencing. The metabolites in serum samples were detected through LC-MS/MS analysis.Results. The composition of gut microbiota in patients exhibited dissimilarities compared to that in healthy subjects, which was distinguished by Prevotella, Slackia, Enterococcus, Bifidobacterium, and Lactobacillales may be potential markers for tracking the progression of hypertension, and Bifidobacterium, Butyricimonas, Adlercreutzia, Faecalibacterium, Lactobacillus, Ruminococcus, Clostridium, and Acidaminococcus demonstrated diagnostic value. Meanwhile, tracking the dynamic changes of deoxycholic acid, 4-oxododecanedioic acid, and l-arginine can serve as biomarkers for early diagnosis, and investigation into the mechanism by which the intestinal microbiome influences the onset and progression of hypertension. In terms of pathogenesis, the findings revealed that Bifidobacterium may caused the changes of AST, indirect bilirubin, ALT, triglyceride and uric acid by affecting metabolites cis-7-hexadecenoic acid methyl ester and N1-acetylspermidine. Additionally, Coprococcus may cause changes in albumin through the influence of androsterone enanthate.Conclusions. These findings highlight that the unique intestinal microbiome and serum metabolic profile in different periods of hypertension will provide valuable insight for timely diagnosis and prognosis tracking in hypertension patients with promising clinical applications.

Cyclometalated Ir(III) Complexes as Lysosome-Targeted Photodynamic Anticancer Agents.

We have designed and synthesized two Ir(III) complexes (Ir1 and Ir2) coordinated with an 8-sulfonamidoquinoline derivative ligand as photosensitizers, which exhibit strong red phosphorescence emission and a long phosphorescence lifetime. The Ir(III) complexes exhibit a high population of triplet states, which enable red phosphorescence and efficient singlet oxygen generation. Ir1 and Ir2 rapidly enter the cancer cells and accumulate in lysosomes, producing large amounts of intracellular singlet oxygen when exposed to light irradiation, eventually leading to cancer cell death, and the phototoxic indexes of complexes Ir1 and Ir2 against cancer cells are in the range of 76-228. Overall, our studies indicate that the synthesized Ir(III) complexes with quinoline ligands exhibit photosensitizing properties, effectively inducing cancer cell death when exposed to light. These promising results suggest their potential application in photodynamic therapy.

Brain natriuretic peptide as a biomarker for predicting contrast-induced nephropathy in patients undergoing coronary angiography/intervention: A systematic review and meta-analysis.

BACKGROUND: Contrast-induced nephropathy (CIN) is associated with adverse events. As there are no effective treatments, the early identification of high-risk patients is required. Individual studies have suggested the utility of brain natriuretic peptide in predicting CIN. Therefore, this meta-analysis aimed to systematically investigate the value of brain natriuretic peptide in predicting CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials Library, and Web of Science from inception date to March 9, 2022. Studies that evaluated the predictive value of brain natriuretic peptide for CIN outcomes in patients after CAG or PCI were included. The quality of the included studies was assessed using the QUADAS-2 tool. Diagnostic accuracy estimates were calculated using a random-effects model. Subgroup and meta-regression analyses were performed to identify the potential sources of heterogeneity. RESULTS: Twelve studies with 7789 patients were included in the meta-analysis. The pooled sensitivity and specificity of brain natriuretic peptide for the prediction of CIN were 0.73 (95% CI: 0.67-0.78) and 0.77 (95% CI: 0.71-0.82), respectively. The area under the summary receiver operating characteristic curve was 0.80 (95% CI: 0.77-0.84). Meta-regression analysis indicated that the sources of sensitivity heterogeneity may be the country, mean age, and study population. Additionally, country, study population, study design, and index text contributed to the specificity heterogeneity. CONCLUSION: This study demonstrated that brain natriuretic peptide could function as a novel potential marker for the early detection of CIN in patients undergoing CAG or PCI.

Exploring the Temporal Correlation of Sarcopenia with Bone Mineral Density and the Effects of Osteoblast-Derived Exosomes on Myoblasts through an Oxidative Stress-Related Gene.

Sarcopenia is an age-related accelerated loss of muscle strength and mass. Bone and muscle are closely related as they are physically adjacent, and bone can influence muscle. However, the temporal association between bone mineral density (BMD) and muscle mass in different regions of the body after adjustment for potential indicators and the mechanisms by which bone influences muscle in sarcopenia remain unclear. Therefore, this study aimed to explore the temporal association between muscle mass and BMD in different regions of the body and mechanisms by which bone regulates muscle in sarcopenia. Here, cross-lagged models were utilized to analyze the temporal association between BMD and muscle mass. We found that low-density lipoprotein (LDL-C) positively predicted appendicular lean mass. Mean whole-body BMD (WBTOT BMD), lumbar spine BMD (LS BMD), and pelvic BMD (PELV BMD) temporally and positively predicted appendicular lean mass, and appendicular lean mass temporally and positively predicted WBTOT BMD, LS BMD, and PELV BMD. Moreover, this study revealed that primary mice femur osteoblasts, but not primary mice skull osteoblasts, induced differentiation of C2C12 myoblasts through exosomes. Furthermore, the level of long noncoding RNA (lncRNA) taurine upregulated 1 (TUG1) was decreased, and the level of lncRNA differentiation antagonizing nonprotein coding RNA (DANCR) was increased in skull osteoblast-derived exosomes, the opposite of femur osteoblast-secreted exosomes. In addition, lncRNA TUG1 enhanced and lncRNA DANCR suppressed the differentiation of myoblasts through regulating the transcription of oxidative stress-related myogenin (Myog) gene by modifying the binding of myogenic factor 5 (Myf5) to the Myog gene promoter via affecting the nuclear translocation of Myf5. The results of the present study may provide novel diagnostic biomarkers and therapeutic targets for sarcopenia.

Ketamine activated glutamatergic neurotransmission by GABAergic disinhibition in the medial prefrontal cortex.

The fast-onset antidepressant actions of ketamine at subanaesthetic doses have attracted enormous interest in psychiatric disease treatment. However, the severe psychotomimetic side effects foster an urgent need to deeply understand the fast-onset antidepressant mechanism of ketamine. Ketamine, as a non-competitive NMDAR antagonist, increases the overall excitability of the mPFC, which is presumed to be essential for the antidepressant action of ketamine. However, the underlying mechanism is still elusive. Here, our results showed that low concentration of ketamine increased the activity and the excitatory/inhibitory ratio of pyramidal neurons; these changes were accompanied by diminished interneurons activity in the mPFC. Moreover, ketamine induced increases in excitatory transmission and antidepressant-like effects, which might rely on the functional intact of GABAergic system in the mPFC. These results suggest a critical role of the mPFC GABAergic system in the fast antidepressant effects of a subanaesthetic dose ketamine.

[Comparison of right atrial matrix metalloproteinase expression between patients with unstable angina and myocardial infarction].

OBJECTIVE: To compare right atrial structural remodeling and the expression of matrix metalloproteinase (MMP) and tissue inhibitors (TIMP) between patients with unstable angina (UA) and myocardial infarction (MI). METHODS: Right atrial appendages were obtained from 18 patients with UA and 22 patients with MI undergoing coronary artery bypass grafting (CABG) operations. MMP-1, -3, -7, -9 and TIMP-1 protein expressions were detected by immunohistochemistry and RT-PCR. Echocardiography was performed before CABG. RESULTS: The left and right atrial diameter, left ventricular diameter and mRNA levels of MMP-3, MMP-9 and TIMP-1 were significantly higher in MI group than those in UA group [LAD: (40.8 +/- 4.2) mm vs. (33.1 +/- 5.1) mm, P < 0.01; RAD: (44.1 +/- 6.8) mm vs. (28.8 +/- 6.0) mm, P < 0.01; LVEDD: (48.9 +/- 6.0) mm vs. (39.7 +/- 7.1) mm, P < 0.05; MMP-3: 0.39 +/- 0.18 vs. 0.28 +/- 0.07, P < 0.05; MMP-9: 0.81 +/- 0.21 vs. 0.55 +/- 0.20, P < 0.01; TIMP-1: 1.79 +/- 0.89 vs. 0.94 +/- 0.47, P < 0.01]. MMP-1, MMP-7 levels were similar between the 2 groups (MMP-1: 0.14 +/- 0.06 vs. 0.10 +/- 0.08, P > 0.05; MMP-7: 0.25 +/- 0.05 vs. 0.23 +/- 0.06, P > 0.05). CONCLUSION: Right atrial up-regulation of MMP-3, MMP-9 and TIMP-1 levels may contribute to the right atrial structural remodeling in MI patients.

Nicorandil effects on platelet function, Hs-CRP, MMP-9 and myocardial antioxidation in patients with unstable angina.

Nicorandil effects on platelet activation and myocardial antioxidant function in patients with unstable angina were studied. A total of 157 patients with unstable angina in the First People's Hospital of Foshan were selected and divided into experimental and control group. Patients in experimental group were treated with conventional drugs and nicorandil (15 min/day), t.i.d., for 21 days as one course of treatment, while those in control group were treated with conventional drugs. After treatment, serum indexes were detected and compared between the two groups of patients. Compared with that in control group, the platelet function of patients in the experimental group was significantly improved, and there was a statistically significant difference (P<0.05). Serum anti-oxidation factors in both groups were increased after treatment, and they were increased more significantly in experimental group (P<0.05). Serum inflammatory factors, high-sensitivity C-reactive protein and matrix metalloproteinase-9, also declined significantly in the experimental group. Nicorandil reduces inflammatory response and promotes stability of myocardial function in the treatment of unstable angina.

Suppression of in vitro and in vivo human ovarian cancer growth by isoacteoside is mediated via sub-G1 cell cycle arrest, ROS generation, and modulation of AKT/PI3K/m-TOR signalling pathway.

PURPOSE: The purpose of the present study was to investigate the anticancer properties of isoacteoside against OVCAR-3 human ovarian cancer cells. Its effects on apoptosis, reactive oxygen species (ROS) generation, cell invasion, cell cycle arrest and its effects on tumor volume and weight were also evaluated in the current study. METHODS: MTT assay was used to study the cytotoxic effects of the compound on the cell viability. Effects on apoptosis and cell cycle arrest were evaluated by flow cytometry. In vitro wound healing assay and matrigel assay were carried out to study the effects of isoacteoside on cell migration and cell invasion respectively. Non-cancer ovarian cell line SV-40 served as control. RESULTS: Isoacteoside exerted both dose-dependent as well as time-dependent growth inhibitory effects on ovarian cancer cells with IC50 values of 15 µM at 24h incubation. Isoacteoside led to early and late apoptosis induction in these cells. Isoacteoside also led to sub-G1 cell cycle arrest which showed strong dose-dependence. Isoacteoside treatment also led to inhibition of cell migration and cell invasion. The results revealed that OVCAR-3 tumor growth was significantly suppressed by isoacteoside administration, compared with that in the control group. At the end of the 5-week period of isoacteoside treatment, the average tumor growth and volume in the untreated control group were considerably higher than those in the treated groups. CONCLUSION: In brief, the current study indicates that isoacteoside has a great potential in suppressing both in vitro and in vivo ovarian cancer cell growth and can be used as a possible anticancer agent.

Pri-miR-34b/c rs4938723 Polymorphism Contributes to Coronary Artery Disease Susceptibility.

OBJECTIVES: Accumulating evidences have shown that polymorphisms in miRNA genes play an important role in the susceptibility to coronary artery disease (CAD). A potentially functional polymorphism rs4938723, which located within the promoter region of pri-miR-34b/c, may affect the expression of miR-34b/c. To date, the role of genetic variant in pri-miR-34b/c on CAD risk is still unknown. Here we aimed to evaluate the association of Pri-miR-34b/c rs4938723 polymorphism with individual susceptibility to CAD in a Chinese Han population. METHODS: Genotyping was performed in a case-control study of 563 patients and 646 controls using polymerase chain reaction-ligase detection reaction (PCR-LDR) method. The association of rs4938723 with CAD risk was evaluated using logistic regression analysis with SPSS software. RESULTS: We found that the C allele of pri-miR-34b/c rs4938723 was significantly associated with a decreased risk of CAD when compared with the T allele (OR = 0.76, 95% CI = 0.62-0.95, p = 0.015). Consistently, compared with those carrying TT genotype, the CC homozygotes displayed significantly reduced risk for CAD (OR = 0.54, 95% CI = 0.32-0.91, p = 0.021). Similar trend of the reduced risk for CAD was detected when the CT and CC genotypes were combined (OR = 0.75, 95% CI = 0.57-0.99, p = 0.044). Stratified analysis of pri-miR-34b/c rs4938723 revealed a more significant association of C allele with decreased CAD risk among older subjects, male and non-smokers. CONCLUSIONS: Our findings suggest that the pri-miR-34b/c rs4938723 polymorphism is associated with CAD susceptibility in the Chinese Han population. Further studies are warranted to confirm the general validity of our findings.

Compound Danshen Dripping Pills pretreatment protects the heart from ischemia/reperfusion injury by enhancing autophagic flux

Abstract Compound Danshen Dripping Pills (CDDPs) have been used in clinical treatment to protect the heart from ischemia/reperfusion (IR) injury for many years. However, the underlying mechanism implicated in the protective effects remains to be explored. Here, we determined the effects of CDDPs in Sprague-Dawley rats with the IR model. Cardiac function in vivo was assessed by echocardiography. Transmission electron microscopy, histological and immunohistochemical techniques, Western blotting and recombinant adeno-associated virus 9 transfection were used to illustrate the effects of CDDPs on IR and autophagy. Our results showed that pretreatment with CDDPs decreased the level of serum myocardial enzymes and infarct size in rats after IR. Apoptosis evaluation showed that CDDPs significantly ameliorated the cardiac apoptosis level after IR. Meanwhile, CDDPs pretreatment increased myocardial autophagic flux, with upregulation of LC3B, downregulation of p62, and increased autophagosomes and autolysosomes. Moreover, the autophagic flux inhibitor chloroquine could increase IR injury, while CDDPs could partially reverse the effects. Furthermore, our results showed that the activation of AMPK/mTOR was involved in the cardioprotective effect exerted by CDDPs. Herein, we suggest that CDDPs partially protect the heart from IR injury by enhancing autophagic flux through the activation of AMPK/mTOR.

Genetic susceptibility of five tagSNPs in the endothelin-1 (EDN1) gene to coronary artery disease in a Chinese Han population.

Endothelin-1 (ET-1) plays important roles in endothelial dysfunction, vascular physiology, inflammation, and atherosclerosis. Nonetheless, the role of ET-1 (EDN1) gene variants on coronary artery disease (CAD) risk remains poorly understood. The aim of the present study was to evaluate the role of EDN1 gene polymorphisms on individual susceptibility to CAD. We genotyped five tagSNPs (single-nucleotide polymorphisms) (rs6458155, rs4145451, rs9369217, rs3087459, and rs2070699) within EDN1 gene in 525 CAD patients and 675 control subjects. In a multivariate logistic regression analysis, we detected an association of rs6458155 in EDN1 gene with the CAD risk; compared with the TT homozygotes, the CT heterozygotes (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.02-2.29, P=0.040) and the CC homozygotes (OR = 1.55, 95% CI = 1.01-2.36, P=0.043) were statistically significantly associated with the increased risk for CAD. A similar trend of the association was found in dominant model (OR = 1.53, 95% CI = 1.05-2.25, P=0.029). Consistently, the haplotype rs6458155C-rs4145451C containing rs6458155 C allele exhibited the increased CAD risk (OR = 1.22, 95% CI = 1.03-1.43, and P=0.018). In addition, CT genotype of rs6458155 conferred the increased plasma ET-1 levels compared with TT genotype (P<0.05). No association of the other four tagSNPs in EDN1 gene with CAD risk was observed. In conclusion, our study provides the first evidence that EDN1 tagSNP rs6458155 is associated with CAD risk in the Chinese Han population, which is probably due to the influence of the circulating ET-1 levels.

The Impact of tagSNPs in CXCL16 Gene on the Risk of Myocardial Infarction in a Chinese Han Population.

CXCL16 has been demonstrated to be involved in the development of atherosclerosis and myocardial infarction (MI). Nonetheless, the role of the CXCL16 polymorphisms on MI pathogenesis is far to be elucidated. We herein genotyped four tagSNPs in CXCL16 gene (rs2304973, rs1050998, rs3744700, and rs8123) in 275 MI patients and 670 control subjects, aimed at probing into the impact of CXCL16 polymorphisms on individual susceptibility to MI. Multivariate logistic regression analysis showed that C allele (OR = 1.31, 95% CI = 1.03-1.66, and P = 0.029) and CC genotype (OR = 1.84, 95% CI = 1.11-3.06, and P = 0.018) of rs1050998 were associated with increased MI risk; and C allele (OR = 0.77, 95% CI = 0.60-0.98, and P = 0.036) of rs8123 exhibited decreased MI risk, while the other two tagSNPs had no significant effect. Consistently, the haplotype rs2304973T-rs1050998C-rs3744700G-rs8123A containing the C allele of rs1050998 and A allele of rs8123 exhibited elevated MI risk (OR = 1.41, 95% CI = 1.02-1.96, and P = 0.037). Further stratified analysis unveiled a more apparent association with MI risk among younger subjects (≤60 years old). Taken together, our results provided the first evidence that CXCL16 polymorphisms significantly impacted MI risk in Chinese subjects.

Variants in ANRIL gene correlated with its expression contribute to myocardial infarction risk.

ANRIL (antisense non-coding RNA in the INK4 locus), located at the 9p21.3 locus, has been known to be closely associated with the risk of coronary artery disease (CAD). To date, studies of the 9p21.3 variants on CAD risk mainly focus on the non-coding region of ANRIL. However, the biological significance of the variants on ANRIL promoter and exons is still unknown. Here we investigate whether the variants on ANRIL promoter and exons have an effect on myocardial infarction (MI) risk, and further analyze the association of these variants with the expression of ANRIL transcript. We did not find any common variants with minor allele frequencies (MAF) larger than 5% in ANRIL promoter by sequencing 1.6kb upstream of the start codon. Unconditional logistic regression analysis revealed that two SNPs in ANRIL exons, rs10965215 and rs10738605, were significantly associated with MI risk. Further studies revealed that ANRIL transcript EU741058.1 expression levels of rs10965215 and rs10738605 risk genotypes were borderline lower than those of protective genotypes. Our data provide the evidence that the variants rs10965215 and rs10738605 in ANRIL exons contribute to MI risk in the Chinese Han population which might be correlated with the expression of its transcript EU741058.1.