Differential expression of microRNAs in aortic tissue and plasma in patients with acute aortic dissection

尖锐大动脉的解剖(AAD ) 的帮助 BackgroundBiomarker 的诊断为诊断和治疗是重要的。然而，为在血的 AAD 的 biomarkers 的鉴定是挑战性的任务 .&#x000a0；这研究的目的是寻找新潜在地，在 AAD.MethodsThe miRNAs 表示的 microRNA (miRNAs ) biomarkers 在登上大动脉的织物和血浆介绍被 microarray 分析在二个集合或组检验。织物组与 AAD 和健康男机关施主的四控制由四个病人组成。没有心血管的疾病，血浆组与 AAD 和 20 控制包括了 20 个病人。生物信息学被用来分析 miRNAs.ResultsOur 学习揭示了的表示的差别的潜在的目标在 AAD 病人，大动脉的织物有 30 差别，这表示了 miRNAs 与 13 起来调整并且 17 下面调整，并且血浆 93 差别表示了 miRNAs， 33 是起来调整的， 60 是下面调整的。四 miRNAs 被发现在 AAD 病人在大动脉的织物和血浆起来调整。预言的 miRNA 目标显示四 dysregulated miRNAs 主要指向了与房间房间粘附，细胞外的矩阵新陈代谢，细胞骨架组织，发炎，和与细胞的 cycles.ConclusionsFour miRNAs 有关的多重发信号小径被联系的基因，它在大动脉的织物并且在在 AAD 病人的血浆是起来调整的，在这研究被识别了。这些 miRNAs 可能是为 AAD 的潜在的诊断 biomarkers。更大的样品调查为进一步的确认被需要。

Molecular analysis for diagnosis of Marfan syndrome and Marfan-associated disorders

Marfan syndrome is a systemic disorder of connective tissue, caused by mutations in the FBN1, TGFBR1 or TGFBR2 genes. This syndrome is characterized by involvement of three major systems, skeletal, ocular, and cardiovascular. The continuing improvements in molecular biology and increasing availability of molecular diagnosis in clinical practice allow recognition of Marfan syndrome in patients with incomplete phenotypes. Additionally, molecular analyses could also be used for preimplantation genetic diagnosis. The identification of a mutation allows for early diagnosis, prognosis, genetic counseling, preventive management of carriers and reassurance for unaffected relatives. The importance of knowing in advance the location of the putative family mutation is highlighted by its straightforward application to prenatal and postnatal screening.

Long Non-coding RNAs Expression Profile in HepG2 Cells Reveals the Potential Role of Long Non-coding RNAs in the Cholesterol Metabolism

Background：Green tea has been shown to improve cholesterol metabolism in animal studies,but the molecular mechanisms underlying this function have not been fully understood.Long non-coding RNAs （lncRNAs） have recently emerged as a major class of regulatory molecules involved in a broad range of biological processes and complex diseases.Our aim was to identify important lncRNAs that might play an important role in contributing to the benefits of epigallocatechin-3-gallate （EGCG） on cholesterol metabolism.Methods：Microarrays was used to reveal the lncRNA and mRNA profiles in green tea polyphenol（-）-epigallocatechin gallate in cultured human liver （HepG2） hepatocytes treated with EGCG and bioinformatic analyses of the predicted target genes were performed to identify lncRNA-mRNA targeting relationships.RNA interference was used to investigate the role of lncRNAs in cholesterol metabolism.Results：The expression levels of 15 genes related to cholesterol metabolism and 285 lncRNAs were changed by EGCG treatment.Bioinformatic analysis found five matched lncRNA-mRNA pairs for five differentially expressed lncRNAs and four differentially expressed mRNA.In particular,the lncRNA4 T102202 and its potential targets mRNA-3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR） were identified.Using a real-time polymerase chain reaction technique,we confirmed that EGCG down-regulated mRNA expression level of the HMGCR and up-regulated expression ofAT102202.After AT102202 knockdown in HepG2,we observed that the level of HMGCR expression was significantly increased relative to the scrambled small interfering RNA control （P 〈 0.05）.Conclusions：Our results indicated that EGCG improved cholesterol metabolism and meanwhile changed the lncRNAs expression profile in HepG2 cells.LncRNAs may play an important role in the cholesterol metabolism.

Role of plasma C-reactive protein and white blood cell count in predicting in-hospital clinical events of acute type A aortic dissection

Background A few recent studies have reported that inflammation is associated with the prognosis of acute aortic dissection （AD）. There is, however, no systemic investigation regarding the role of plasma C-reactive protein （CRP） and white blood cell （WBC） levels in predicting in-hospital clinical events of acute type AAD. Methods The levels of high-sensitivity CRP and WBC counts were systemically determined after admission in 36 patients with acute type A AD. The variations of plasma CRP and WBC levels in different time windows （admission, 1, 2, 3, 4, 6, 8 days） in patients with acute type AAD were analyzed between patients with events and without events. Results During hospitalization, five patients died, and increased levels of CRP and WBC were found in patients died with acute type A AD compared with patients survived （P 〈0.01, respectively）. Medical treatment may significantly decrease inflammatory response in survived patients with acute type A AD. Additionally, patients with complication of pleural effusion showed higher CRP and WBC levers （P=0.046, P=-0.018, respectively）. Lower WBC levels were found in survived patients treated medically （P=-0.001）. Moreover, mean CRP and WBC levels had positive correlations with aortic diameter （r=0.364, P--0.000; r=0.333, P=0.000, respectively） and age （r=0.270, P=0.000, respectively）, while negative correlations with the time from onset of symptoms to hospital admission （r= -0.229, P=0.000, r= -0.200, P=0.002, respectively）. Univariate analysis showed that age 〉65 years, CRP zl 2.05 rag/L, WBC 〉12.16×10^9/L, aortic diameter 〉48 mm, pleural effusion and diastolic blood pressure 〉105 mmHg were associated with hospital mortality. While CRP 〉12.05 mg/L, WBC ≥12.16×10^9/L, aortic diameter 〉48 mm were strongly associated with hospital mortality in multiple Logistic regression analysis. Conclusions The results suggested that CRP and WBC were preferred markers for predicting the clinical events in patients with acute type A AD, especially death during hospitalization. Therefore, further study enrolling larger cohort, prospective study would be warranted.

Prevalence and risk factors for left ventricular hypertrophy and left ventricular geometric abnormality in the patients with hypertension among Han Chinese

Background Left ventricular hypertrophy （LVH） and geometric abnormality are associated with morbidity and mortality of cardiovascular disease and stroke. Hypertension is the major cause of LVH. Yet the prevalence and other risk factors of LVH and geometric abnormality in Chinese hypertensive population are unknown. The objective of this study was to investigate the prevalence and risk factors of LVH and geometric abnormality in community-based Chinese hypertensive population. Methods The study was a community-based cross-sectional study, and comprised 4270 hypertension patients with integrated clinical and echocardiographic data. Left ventricular mass was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of over 49.2 g/m^2.7 for men and 46.7 g/m^2.7 for women. LV geometric patterns （normal, concentric remodeling, concentric or eccentric hypertrophy） were calculated according to LVH and relative wall thickness. Logistic regression model was used to determine the odds ratio （OR） and 95% confidence intervals （CI） of the risk factors of LVH. Results The prevalence of LVH was 42.7% in 4270 hypertensive patients, with 37.4% in males and 45.4% in females, respectively. The prevalence of concentric remodeling, concentric or eccentric hypertrophy was 24.7%, 20.2%, and 22.6%, respectively. In Logistic regression model, female （OR 1.3, 95%C/ 1.1-1.5, P 〈0.01）, age （OR 1.02, 95%C/ 1.01-1.03, P 〈0.01）, body mass index （OR 1.2, 95%C/1.15-1.20, P 〈0.01）, systolic blood pressure （OR 1.02, 95%C/ 1.01-1.03, P 〈0.01 ）, and serum triglyceride （OR 1.10, 95% CI 1.00-1.20, P 〈0.01 ） were risk factors of LVH. Female, age, body mass index, systolic blood pressure and serum triglyceride were also risk factors of left ventricular geometric abnormality. Conclusions The echocardiographic LVH is the major complication of patients with hypertension in rural area of China, especially for women. To effectively treat hypertension, weight loss and control of serum triglyceride may help to prevent LVH in hypertensive population.

Polymorphisms of angiotensin-converting enzyme 2 gene associated with magnitude of left ventricular hypertrophy in male patients with hypertrophic cardiomyopathy

Background Even carrying an identical gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hypertrophic cardiomyopathy （HCM）. Modifier genes may contribute to the diversity. Angiotensin-converting enzyme 2 （ACE2） gene has been established to be associated with parameters of left ventricular hypertrophy in community based male subjects. The objective of the present study was to investigate the association of ACE2 gene polymorphisms with the phenotype of HCM. Methods A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. The polymorphism of rs2106809 and rs6632677 were genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and confirmed by sequencing. Logistic regression model and multivariate analysis were used to determine the odds ratio （OR） and 95% confidence intervals （CO of variations of ACE2 for HCM. Results The T allele of rs2106809 and C allele of rs6632677 conferred increasing risk for HCM （OR 1.34, 95%C/ 1.01-1.77, P=0.04; OR 1.11, 95%C/ 1.03-1.21, P=0.002, respectively）, and the 2 single nucleotide polymorphisms （SNPs） were in strong linkage disequilibrium （LD）, the TC haplotype was independently associated with a higher OR for HCM （OR=1.59, 95%C/1.21-1.87） after adjusted for conventional risk factors. And the risk alleles were associated with thicker interventricular septal thickness of HCM （（20.0±6.3） mm vs （17.9±5.5） mm, P=0.03 and （21.3±5.9） mm vs （17.9±5.8） mm, P=0.04, respectively）. No association was found between the two polymorphisms with female patients with HCM. Conclusion Minor alleles of ACE2 gene might be the genetic modifier for the magnitude of left ventricular hypertrophy in male patients with HCM.

Protective effect of chrysoeriol against doxorubicin-induced cardiotoxicity in vitro

Background The use of doxorubicin （DOX） is limited by its dose-dependent cardiotoxicity. Reactive oxygen species （ROSs） play an important role in the pathological process of DOX-induced cardiotoxicity. The aim of this study was to evaluate the protective effect of chrysoeriol, a flavone compound, against DOX-induced apoptosis and death in H9c2 cells and to find out its preliminary mechanism. Methods We used 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tetrazolium bromide （MTT） assay, Hoechst33258 staining and measurement of lactate dehydrogenase （LDH） release to evaluate the protective effect of chrysoeriol against DOX-induced apoptosis and death in H9c2 cells. To find out the mechanism of this protective effect, we observed the immunofluorescence of intracellular ROS and measured the activities of malondialdehyde （MDA）, superoxide dismutase （SOD） and glutathione peroxidase （GPx）. Furthermore, we evaluated the effect of chrysoeriol on the antitumor activity of DOX in HeLa cells with MTT assay. Results The results of MTT assay, Hoechst 33258 staining and measurement of LDH release showed that chrysoeriol significantly reduced doxorubicin-induced apoptosis and cell death. Chrysoeriol at a dose of 20 μg/ml notably reduced intracellular ROS, decreased the concentration of MDA in the supernatant of DOX-treated H9c2 cells and increased SOD and GPx activities to their normal levels. Further study showed that the addition of chrysoeriol did not affect the antitumor activity of DOX. Conclusion Chrysoeriol could potentially serve as a novel cardioprotective agent against DOX-induced cardiotoxicity without affecting the antitumor activity of DOX.

Variants of tumor necrosis factor-induced protein 3 gene are associated with left ventricular hypertrophy in hypertensive patients

Background Tumor necrosis factor-induced protein 3 （TNFAIP3） gene has been shown important in cardiac remodeling. The aim of the present study was to investigate whether the variants of TNFAIP3 gene are associated with left ventricular hypertrophy （LVH） in hypertensive patients.Methods Four representatives of all the other single nucleotide polymorphisms （SNPs） in TNFAIP3 gene were tested for association with hypertrophy in two independent hypertensive populations （n=2120 and n=324）.Results We found that only the tag SNP （rs5029939） was consistently lower in the hypertensives with cardiac hypertrophy than in those without cardiac hypertrophy in the two study populations, indicating a protective effect on LVH （odds ratio （OR） （95% confidence interval （CI））0.58 （0.358-0.863）, P=0.035; OR （95% CI）=0.477 （0.225-0.815）, P〈0.05,respectively）. Multiple regression analyses confirmed that the patients with G allele of rs5029939 had less thickness in inter-ventricular septum, left ventricular posterior wall, relative wall thickness and left ventricular mass index than did those with CC allele in the hypertensive patients in both study populations （all P〈0.01）.Conclusion These findings indicate that the SNP （rs5029939） in the TNFAIP3 gene may serve as a novel protective genetic marker for the development of LVH in patients with hypertension

Cardiovascular risk and prevalence of metabolic syndrome by differing criteria

Background The prevalence of metabolic syndrome （MetS） in hypertensive population in Chinese countryside is unknown. Firstly, this study compared the prevalence of MetS according to National Cholesterol Education Program （NCEP） ATPIII, revised NCEP and International Diabetes Federation （IDF） definitions. Secondly, it investigated the association between MetS, coronary heart disease （CHD） and stroke in patients with hypertension. Methods In this cross sectional study, the cluster sampling method was used. Three MetS definitions were applied to 1418 normal subjects and 5348 hypertensive patients aged 40-75 years in rural areas in China. The agreement between different MetS definitions was estimated by K statistics. Logistic regression analyses determined the association between MetS defined by the three MetS definitions and CHD and stroke. Results In subjects without hypertension, the prevalence of Mets was 4.1% by NCEP definition, 8.3% revised NCEP definition and 7.8% IDF definition. In hypertensive individuals, the prevalence was 14.0%, 32.9%, and 27.4% in men; 35.6%, 53.1%, and 50.2% in women by the same definitions, respectively. In hypertensive individuals, the agreement was 94.4% in men and 97.0% in women between revised NCEP and IDF definitions. The IDF defined MetS was more strongly associated with CHD than the NCEP or revised NCEP defined MetS （adjusted odds ratio： 1.92 compared with 1.85 and 1.69 in men; 1.64 compared with 1.48 and 1.60 in women）. Conclusions In the patients with hypertension, the revised NCEP and IDF definitions identified more individuals than NCEP definition and their agreement is very high. The IDF defined MetS is more strongly associated with CHD than the NCEP or revised NCEP defined MetS, but weakly or not associated with stroke.

Fish consumption and incidence of heart failure： a meta-analysis of prospective cohort studies

Background The association between fish consumption and heart failure （HF） incidence is inconsistent. Methods We performed a systematic search of Pubmed and Embase （from 1953 to June 2012） using key words related to fish and HF. Studies with at least three categories of fish consumption reporting both relative risk （RR） and corresponding 95% confidence interval （CI） for HF incidence were included. The pooled RR and 95%C/were calculated using a fixed or random-effects model. The generalized least squares regression model was used to quantify the dose-response relationship between fish consumption and HF incidence. Results Five prospective cohort studies including 4750 HF events of 170 231 participants with an average of 9.7-year follow-up were selected and identified. Compared with those who never ate fish, individuals with higher fish consumption had a lower HF incidence. The pooled RRs for HF incidence was 0.99 （95%CI, 0.91 to 1.08） for fish consumption 1 to 3 times per month, 0.91 （95%CI, 0.84 to 0,99） for once a week, 0.87 （95%CI, 0.81 to 0.95） for 2 to 4 times per week, and 0.86 （95% CI, 0.84 to 0.99） for 5 or more times per week. An increment of 20 g of daily fish intake was related to a 6% lower risk of HF （RR： 0.94, 95% CI, 0.90 to 0.97; P for trend = 0.001）. Conclusions This meta-analysis suggests that there is a dose-dependent inverse relationship between fish consumption and HF incidence. Fish intake once or more times a week could reduce HF incidence.

Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population

Background The ghrelin plays an important role in the regulation of food intake and energy homeostasis. Therefore, the ghrelin receptor gene （GHSR） is an excellent candidate for studying metabolic syndrome. This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population. Methods Subjects consisted of 698 patients aged 41 to 80 years, diagnosed as metabolic syndrome by International Diabetes Federation （IDF） 2005 criteria, and 762 age- and gender-matched controls. Three variants within the GHSR were selected and genotyped using polymerase chain reaction （PCR） and restriction fragment length polymorphism （RFLP）. Odds ratios were estimated using a case-control study design by controlling confounding factors. Results The NA genotype （rs2922126） in the promoter was associated with metabolic syndrome （OR 1.41, 95%C/ 1.03-1.94）, increased waist circumference （OR 1.75, 95%C/1.26-2.42）, and increased fast blood glucose （OR 1.49, 95%CI 1.07-2.06） in women. The NA genotype （rs509030） in the intron was associated with lower plasma high density lipoprotein in women （OR 1.37, 95%C/1.02-1.84）. Conclusion The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.

Identification of a novel lethal fibrillin-1 gene mutation in a Chinese Marfan family and correlation of 3＇ fibrillin-1 gene mutations with phenotype

Background Mutations in the fibrillin-1 gene have been identified in patients with Marfan syndrome （MFS）. This study aimed to identify the molecular defects in the fibrillin-1 gene in a Chinese family with Marfan syndrome, accompanied by aortic aneu rysms/dissection. Methods Two patients and one non-carrier in the family underwent complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of these individuals in the family as well as 50 healthy normal controls. Polymerase chain reaction amplification and direct sequencing of all 65 coding exons of fibrillin-1 gene were analyzed. Results We found a novel mutation （c.8547T〉G, p.Tyr2849X） in exon 65 of fibrillin-1 gene in a Chinese proband with Marfan syndrome, accompanied by aortic aneurysms/dissection. Sudden death at a young age of affected members was seen due to aortic aneurysms/dissection. By evaluating genotype-phenotype correlations of patients with mutations in the 3＇ end of fibrillin-1 gene （exons 64 and 65）, we also found that the presence of nonsense mutations occurring in exons 64 and 65 appeared to be an indicator of early-onset aortic risk and sudden death. Conclusions These results expand the mutation spectrum of fibrillin-1 gene and help in the study of the molecular pathogenesis of Marfan syndrome, indicating that mutations occurring in the 3＇ end of fibrillin-1 gene may play an independent functional role in the pathogenesis of Marfan syndrome.

Genetic diagnosis of Liddle＇s syndrome by mutation analysis of SCNN1B and SCNN1G in a Chinese family

Background Liddle＇s syndrome is a rare autosomal-dominant monogenic form of salt-sensitive hypertension. This study aimed to screen the gene mutation in 13 and y subunits of the epithelial sodium channel （ENaC） of a Chinese family with Liddle＇s syndrome, an autosomal dominant form of hypertension. Methods DNA samples from the proband with early-onset, treatment-resistant hypertension and suppressed plasma renin activity were initially screened for mutations in the C-terminal exons of the ENaC 13 or y subunit genes, using amplification by polymerase chain reaction and direct DNA sequencing. We also screened the C-terminus of SCNNIB and SCNNIG in family members, and screened for the mutation in 150 controls. Results Genetic analysis of the 13 ENaC gene revealed a missense mutation of CCC to TCC at codon 616 in the proband, her mother and her grandmother. One hundred and fifty randomly selected controls had not the mutation, indicating that this is not a common genetic polymorphism. There was no mutation of the y ENaC gene in any of the individuals examined. Conclusions Through direct DNA sequencing analysis, we established the diagnosis of Liddle＇s syndrome for the proband and her families, and provided tailored therapies to this abnormality. These results provide further evidence that Pro616Ser is a critical amino acid that has a key role in the inhibition of sodium channel activity.

Febuxostat, a nonpurine selective inhibitor of xanthine oxidase： a promising medical therapy for chronic heart failure？

Heart failure is currently one of the most common and most cost-intensive of the chronic diseases The main cause of chronic heart failure （CHF） is the abnormalities of both cardiac contractile performance and myocardial energy metabolism. Elevated levels of reactive oxygen species （ROS） have been proposed to contribute to both of them. Xanthine oxidoreductase （XO） is a major source of ROS in the cardiovascular system. XO inhibitors （XOIs） have been the cornerstone of the clinical management of gout and conditions associated with hyperuricemia for several decades.

Genetics of ischemic and hemorrhagic stroke in Chinese population

Stroke is a major cause of adult death and disability worldwide.Epidemiological and animal studies have provided strong evidence that the pathogenesis of stroke is multi-factorial and induced by a combination of environmental and genetic risk factors,but the identifica-tion of individual causative variants remains little known.Genetic influences are likely to be polygenic with small effect sizes,and stroke itself consists of a number of different subtypes which may each have different genetic profiles.In addition,various ethnic populations may have different stroke risk,such as Asian race.The reasons for high risk of stroke among the Chinese,especially hemorrhagic stroke,remain unknown.Most human studies have taken a candidate gene approach using case-control methodology.To be reliably detected,small relative risks require large sample sizes,probably 1000 patients or more.Genome-wide association(GWA)study is an unbiased and comprehensive approach to identify common risk alleles for complex diseases.Recently,a multistage GWA study has identified three loci on chromosomes 2q,8q and 9p to be associated with intracranial aneurysm in European and Japanese populations.Another GWAfinding is the identification of risk variants for cardioembolic stroke on chromosome 4q25 in European populations.In this review,we mainly focus on the results from case-control association studies on genetic factors that play a role in the risk of ischemic and hemorrhagic stroke in Chinese population.The combined effects of multiple susceptibility genes for stroke risk are also summarized.