Association between rs20456 and rs6930913 of Kinesin-Like Family 6 and Hypertension in a Chinese Cohort.

This study aimed to investigate the relationship between kinesin-like family 6 (KIF6) polymorphisms and hypertension in a northeast Chinese cohort. In this study, two single nucleotide polymorphisms of KIF6 (rs20456 and rs6930913) and their haplotype were analyzed in 382 hypertension patients and 378 controls with SHEsis analysis platform, and the gene-environmental interactions were evaluated with logistic regression analysis. After adjusting for confounding factors, significantly lower risk of hypertension was observed in participants with genotype TC (0.416 (CI 0.299-0.578), p < 0.001) and CC (0.577 (0.389-0.857), p=0.007) of rs20456 compared with TT. For rs6930913, allele T (0.522 (0.386-0.704), p < 0.001), genotype TT (0.325 (0.205-0.515), p < 0.001), and genotype CT (0.513 (0.379-0.693), p < 0.001) were significantly associated with lower risk of hypertension than allele C and CC genotype, respectively. Gene-environment analyses confirmed the significant influence on hypertension by the interactions between genotypes distribution in rs20456 (CT: p=0.036, TT: p=0.022) and smoking status. No interactions were found between smoking and rs6930913, except those with dominant or recessive genetic models (both P s =0.006). There were no interactions between KIF6 and overweight (all P s > 0.05). Haplotype analyses showed that CC (p=0.005) and TC (p=0.001) of rs20456 and rs6930913 were significantly associated with a statistically increased risk of hypertension. The false-positive report probability (FPRP) analysis was used to verify significant findings. In conclusions, KIF6 might affect the susceptibility of hypertension. The allele C (rs20456) and allele T (rs690913) were inclined to protect individuals from hypertension both in genotype and haplotype analyses.

Value of reduced glomerular filtration rate assessment with cardiometabolic index: insights from a population-based Chinese cohort.

BACKGROUND: Recent studies have suggested that cardiometabolic index (CMI), a novel estimate of visceral adipose tissue, could be of use in the evaluation of cardiovascular risk factors. However, the potential utility and clinical significance of CMI in the detection of reduced estimated glomerular filtration rate (eGFR) remains uncertain. The purpose of this study was to investigate the usefulness of CMI in assessing reduced eGFR in the general Chinese population. METHODS: This cross-sectional analysis included 11,578 participants (mean age: 53.8 years, 53.7% females) from Northeast China Rural Cardiovascular Health Study (NCRCHS) of general Chinese population (data collected from January 2013 to August 2013). CMI was calculated by triglyceride to high density lipoprotein cholesterol ratio multiply waist-to-height ratio. Reduced eGFR was defined as eGFR< 60 ml/min per 1.73m2. Multivariate regressions were performed to determine CMI's association with eGFR value and eGFR reduction, ROC analyses were employed to investigate CMI's discriminating ability for decreased eGFR. RESULTS: The prevalence of reduced eGFR was 1.7% in males and 2.5% in females. CMI was notably more adverse in reduced eGFR groups, regardless of genders. In fully adjusted multivariate linear models, each 1 SD increment of CMI caused 3.150 ml/min per 1.73m2 and 2.411 ml/min per 1.73m2 loss of eGFR before CMI reached 1.210 and 1.520 in males and females, respectively. In logistic regression analyses, per 1 SD increase of CMI brought 51.6% additional risk of reduced eGFR in males while caused 1.347 times of risk in females. After divided into quartiles, people in the top quartile of CMI had higher adjusted ORs of having reduced eGFR, with ORs of 4.227 (1.681, 10.627) and 3.442 (1.685-7.031) for males and females respectively. AUC of CMI was revealed to be 0.633 (0.620-0.646) in males and 0.684 (0.672-0.695) in females. CONCLUSIONS: Higher CMI was independently associated with greater burden of reduced eGFR, highlighting VAT distribution and dysfunction as a potential mechanism underlying the association of obesity with kidney damage and adverse cardiovascular outcomes. The findings from this study provided important insights regarding the potential usefulness and clinical relevance of CMI in the detection of reduced eGFR among general Chinese population.

Association of rs2271037 and rs3749585 polymorphisms in CORIN with susceptibility to hypertension in a Chinese Han population: A case-control study.

Corins are membrane-bound protease that regulates blood pressure by activating the natriuretic peptides. These pro-atrial natriuretic peptide convertases are essential for sodium homeostasis and normal blood pressure. CORIN variants have been identified in humans and other animals, but no studies of CORIN polymorphisms have been conducted in northeastern China. This study aims to investigate the association of 2 single nucleotide polymorphisms (SNPs) in CORIN (rs2271037 and rs3749585) with hypertension, as well as their potential interactions with some risk factors of hypertension in a Han population of northeastern China. A case-control study, including 402 patients with hypertension and 406 participants with normal blood pressure, was conducted in Liaoning province. SNP genotyping was carried out by high resolution melting (HRM) after polymerase chain reaction amplifications. Since rs3749585 is located in 3' untranslated region (UTR) of CORIN, in silico analysis was used to predict target micro RNAs on TargetScan, miRanda, and DIANA-microT. As a result, mutant T allele in rs2271037 (odds ratio [OR], 1.693; 95% confidence [CI], 1.528-1.877; p < 0.001) and C allele in rs3749585 (OR, 1.114; 95% CI 1.011-1.227; p = 0.029) increased the risk of hypertension, comparing with wild G allele and T allele, respectively. Patients with genotype TT (OR, 10.209; 95% CI, 6.414-16.250; p < 0.001) and GT (OR, 1.730; 95% CI, 1.226-2.443; p = 0.002) have higher risk of hypertension than those with genotype GG. SNP rs2271037 was significantly associated with susceptibility to hypertension in all genetic models (dominant model: OR, 2.879; 95% CI, 2.080-3.986; p < 0.001; recessive model: OR, 7.159; 95% CI, 4.779-10.724; p < 0.001; additive model: OR, 1.535; 95% CI, 1.163-2.027; p = 0.002). SNP rs3749585 was significantly correlated with hypertension susceptibility only in dominant model (OR, 1.533; 95% CI, 1.073-2.189; p = 0.019), but not in recessive model (OR, 1.220; 95% CI, 0.906-1.644; p = 0.191) or additive model (OR, 0.915; 95% CI, 0.694-1.205; p = 0.527). After adjusting for age, gender, body mass index (BMI), smoking, low-density lipoprotein cholesterol, and serum sodium level in logistic models, the same statistical results were obtained. Interaction study showed the association between CORIN polymorphisms and hypertension could be changed by overweight (BMI ≥ 25 kg/m2). In silico analyses implicated hsa-miR-495 as a target miRNA that potentially interacts with the 3' UTR of CORIN. In conclusion, polymorphisms of rs2271037 and rs3749585 in CORIN were significantly associated with hypertension in a Han population of northeastern China. The mutant-type T allele of rs2271037 and C allele of rs3749585 might increase the susceptibility to hypertension in this population.

Prediction of marker genes associated with hypertension by bioinformatics analyses.

This study aimed to explore the underlying marker genes associated with hypertension by bioinformatics analyses. A gene expression profile (GSE54015) was downloaded. The differentially expressed genes (DEGs) between the normotensive female (NF) and hypertensive female (HF), and between the normotensive male (NM) and hypertensive male (HM) groups were analyzed. Gene Ontology (GO) and pathway enrichment analyses were performed, followed by protein-protein interaction (PPI) network construction. The transcription factors (TFs), and the common DEGs between the HF and HM groups were then analyzed. In total, 411 DEGs were identified between the HF and NF groups, and 418 DEGs were identified between the HM and NM groups. The upregulated DEGs in the HF and HM groups were enriched in 9 GO terms, including oxidation reduction, such as cytochrome P450, family 4, subfamily b, polypeptide 1 (Cyp4b1) and cytochrome P450, family 4, subfamily a, polypeptide 31 Cyp4a31). The downregulated DEGs were mainly enriched in GO terms related to hormone metabolic processes. In the PPI network, cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) had the highest degree in all 3 analysis methods in the HF group. Additionally, 4 TFs were indentified from the 2 groups of data, including sterol regulatory element binding transcription factor 1 (Srebf1), estrogen receptor 1 (Esr1), retinoid X receptor gamma (Rxrg) and peroxisome proliferator-activated receptor gamma (Pparg). The intersection genes were mainly enriched in GO terms related to the extracellular region. On the whole, our data indicate that the DEGs, Cyp4b1, Cyp4a31 and Loxl2, and the TFs, Esr1, Pparg and Rxrg, are associated with the progression of hypertension, and may thus serve as potential therapeutic targets in this disease.

Efficacy and safety of ticagrelor versus clopidogrel with different dosage in high-risk patients with acute coronary syndrome.

BACKGROUND: Dual antiplatelet therapy is recommended as a standard antiplatelet strategy in acute coronary syndrome. For those with reduced pharmacologic response to clopidogrel, strengthening antiplatelet therapy (clopidogrel 150mg daily) may reduce adverse clinical events. Ticagrelor is a direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and offset than clopidogrel. METHODS: In this retrospective study, we compared ticagrelor (180mg loading dose 90mg twice daily thereafter), clopidogrel (300mg loading dose, 75mg or 150mg daily thereafter) for the prevention of cardiovascular events in 273 high-risk patients admitted to coronary care unit with acute coronary syndrome. RESULTS: The rate of IST in hospital was significantly reduced in patients of ticagrelor group comparing with those receiving clopidogrel 75mg (0.69% vs 8.2%, p=0.009). Moreover, the TVR rate was less in the ticagrelor group than clopidogrel 75mg group (2.7% vs 13.1%, p=0.007) 6months follow-up. The incidence of MACCE has no difference between the two clopidogrel groups. Kaplan-Meier analysis of MACCE-free indicated that there was no difference between the three groups. Ticagrelor significantly increased the rate of minor bleeding compared with clopidogrel 75mg daily during hospital (45.5% vs 26.2%,p=0.012) and 6-month follow-up (66.9% vs 45.9%,p=0.004).Bleeding-free prognosis was significantly better in the clopidogrel 75mg daily group. CONCLUSIONS: In patients with acute coronary syndrome undergoing PCI, the rate of in-stent thrombosis and TVR were significantly reduced treated with ticagrelor compared with clopidogrel 75mg daily, without an increase of overall major bleeding, but with an increase of minor bleeding.

Bioinformatics Analyses of Differentially Expressed Genes Associated with Acute Myocardial Infarction.

BACKGROUND: We aimed to predict key genes associated with acute myocardial infarction (AMI) by bioinformatics analysis. METHODS: The microarray data of GSE48060, including peripheral blood samples from 31 first-time AMI patients within 48-h post-MI and 21 normal controls, were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) in AMI samples compared with normal controls were identified. Functional enrichment analysis was then performed, followed by analysis of protein-protein interaction (PPI) network and transcription regulatory network (TRN). RESULTS: A total of 385 up- and 504 down-regulated DEGs were identified. They were mainly enriched in five pathways, such as natural killer (NK) cell-mediated cytotoxicity and chemokine signaling pathway. Chemokine (C-C motif) ligand 5 (CCL5) was hub protein in PPI network. Besides, four transcription factors (TFs), including nuclear receptor subfamily 2, group C, member 2 (NR2C2), MYC-associated factor X (MAX), general transcription factor IIIC, polypeptide 2, beta 110 kDa (GTF3C2), and B-cell CLL/lymphoma 3 (BCL3), were identified. Notably, nuclear receptor coactivator 7 (NCOA7) interacted with GTF3C2 and MAX directly. CONCLUSIONS: CCL5, BCL3, NR2C2, MAX, GTF3C2, and NCOA7 might play important roles in AMI development.

Prevalence of atrial fibrillation and its risk factors in rural China: a cross-sectional study.

OBJECTIVES: To evaluate the prevalence of atrial fibrillation (AF) in physical laborers in rural China and identify contributing risk factors. METHODS: A cross-sectional study of 11,956 permanent residents of Liaoning Province in rural China≥35y of age (primarily physical laborers) was conducted between January and August 2013 (response rate 85.3%). All participants completed a questionnaire and underwent a physical exam, echocardiography and electrocardiography. Blood samples were drawn for laboratory analyses, and AF was diagnosed on the basis of history and electrocardiograph findings. Risk factors for AF were evaluated with a stepwise logistic regression analysis. RESULTS: The prevalence of AF was 1.2% overall, but rose steeply with age (0.1% in those 35-44y of age, and 4.6% in those≥75y); there was no significant gender difference at any age. Independent risk factors for AF were age (odds ratio [OR] 1.89; P<0.001), diabetes (OR 2.07; P=0.001), history of myocardial infarction (OR 5.91; P<0.001), low left ventricular ejection fraction (OR 1.85; P=0.005), and low physical activity (OR 1.72; P=0.003), whereas obesity, hypertension, cholesterol and triglyceride levels, current smoking and drinking, left ventricular hypertrophy, and family history of AF were not significant contributors. CONCLUSIONS: Although the prevalence of AF in physical labors in rural China is low, age, diabetes, history of myocardial infarction, low left ventricular ejection fraction, and low physical activity are independent risk factors.

High prevalence of dyslipidemia and associated risk factors among rural Chinese adults.

BACKGROUND: Dyslipidemia is a key independent modifiable risk factor for Cardiovascular Disease, which is a leading contributor to morbidity and mortality in most developed and developing countries. This study was designed to investigate the current epidemiological features of dyslipidemia among adults in rural China. METHODS: Between January 2013 and August 2013, we conducted a cross-sectional study involving 11,956 subjects with age≥35 years in a general Chinese population. Permanent residents of the population were invited to participate in the study and the response rate was at 85.3%. Dyslipidemia was identified based on serum lipids levels following the standards proposed by the National Cholesterol Education Program Adult Treatment Panel III. Multivariate logistic regression analysis was used to evaluate the associated risk factors for dyslipidemia. RESULTS: Within the study population, 16.4% had high TC, 13.8% had low HDL-C, 7.6% had high LDL-C, and 17.3% had high TG concentrations. Prevalence of lipid abnormality (including borderline dyslipidemia and dyslipidemia) was 47.8%, 13.8%, 25.7% and 30.7% for TC, HDL-C, LDL-C and TG, respectively. Detailed analysis indicated that 36.9% of this population had at least one type of dyslipidemia and 64.4% had at least one type of abnormal lipid concentration. Thus, this study observed an alarmingly higher prevalence of lipid abnormality, in a relatively large population, compared to previous studies. Further, we determined that not all of the risk factors studied, including age, gender, hypertension, diabetes mellitus, obesity, smoking, drinking, education level, marital status, and family income, influenced dyslipidemia to the same extent. CONCLUSIONS: Our present study, in a population of 11,956 adults in Liaoning Providence, demonstrated a very high prevalence of dyslipidemia, which represented an alarming rise since the publication of our previous study and other similar studies around the world, which report lower levels. We also examined various risk factors for dyslipidemia, many of which are modifiable risk factors for Cardiovascular Disease (CVD), to provide a comprehensive view that will help in designing strategies to slow the rapid spread and promote effective measures to treat dyslipidemia. Our ultimate goal is to prevent the increasing prevalence of lipid abnormality and reduce the burden of CVD in rural China.

Fluoxetine inhibits monocrotaline-induced pulmonary arterial remodeling involved in inhibition of RhoA-Rho kinase and Akt signalling pathways in rats.

Activation of the small GTPase Ras homolog gene family member A (RhoA) and Rho-associated kinase (ROCK) are important in the pathogenesis of pulmonary arterial hypertension (PAH). Selective serotonin reuptake inhibitors inhibit activation of RhoA and ROCK in vitro, and ameliorate PAH and pulmonary arterial remodeling in vivo. However, little is known about whether the RhoA-ROCK signalling pathway is involved in the treatment of PAH with fluoxetine in vivo. The aim of the present study was to investigate the involvement of the RhoA-ROCK signalling pathway in the protective effect of the selective serotonin reuptake inhibitor fluoxetine against monocrotaline (MCT)-induced pulmonary arterial remodeling. MCT was applied to establish PAH in male Wistar rats. Fluoxetine was administered by gastric gavage once a day for 21 d. The results showed that MCT induced pulmonary arterial remodeling, raised the serotonylation and membrane translocation of RhoA in the lungs, and increased serotonin transporter (5-HTT), RhoA, and ROCK2 expression, and extracellular signal-regulated kinase (ERK) and Akt phosphorylation in the pulmonary arteries and the lungs. Fluoxetine markedly inhibited these MCT-induced changes. The findings suggest that fluoxetine inhibits MCT-induced pulmonary arterial remodeling in rats by inhibition of the RhoA-ROCK and Akt signalling pathways.

[Primary risk factors in Chinese patients with first acute myocardial infarction].

OBJECTIVE: To analyze the primary risk factors of patients with first ST elevation acute myocardial infarction (FSTEMI) in Beijing and Shenyang area between 2004--2005. The Attributable risk percentage (ARP) and population attributable risk percentage (PARP) of every risk factor were determined. METHOD: A total of 426 consecutive FSTEMI patients and 426 gender and age matched healthy controls were included in this 1:1 matched case-control study. RESULT: Multivariate logistic regression analysis showed that following 8 primary risk factors were associated with FSTEMI: heavy smoking (OR = 3.170), diabetes (OR = 2.835), positive family history (OR = 2.243), lack of soybeans intake (OR = 2.243), higher psychological stress (OR = 2.138), lack of fish intake (OR = 1.740), lower education level (OR = 1.572) and recent adverse life events (< 6 months before FSTEMI, OR = 1.515). The ARP are 71.53%, 58.33%, 54.05%, 40.81%, 56.85%, 41.53%, 48.62%, 54.00%; the PARP are 38.79%, 10.40%, 4.69%, 33.72%, 36.03%, 24.96%, 29.56%, 14.83%, respectively. CONCLUSION: In this patient cohort, the harmful risk factors responsible for the development of FSTEMI in Beijing and Shenyang areas during 2004--2005 are heavy smoking, higher psychological stress, lack of soybeans intake, lower education level, lack of fish intake, recent adverse life events, diabetes and positive family history.

[Remote postconditioning by brief renal ischemia and reperfusion reduces acute myocardial ischemia and reperfusion induced myocardial apoptosis in rabbits].

OBJECTIVES: To observe the effects of renal ischemic postconditioning (RI-Post) on myocardial apoptosis in rabbits with acute myocardial ischemia and reperfusion. METHODS: All rabbits were subjected to 60 minutes ischemia by left anterior descending coronary artery occlusion (LADO) and 6 hours reperfusion. The rabbits are randomly divided into 3 groups (n = 8 in each group): (1) Ischemia-reperfusion (IR): LADO and reperfusion without additional intervention; (2) RI-Post: after 60 minutes of LADO, the left renal artery was occluded for 30 seconds and reperfused for 30 seconds and repeated 3 times, then the coronary artery was reperfused for 6 hours; (3) Medication intervention (MI): 10 minutes before coronary reperfusion, rabbits were treated with PKC antagonist GF109203X (0.05 mg/kg, IV), followed by RI-Post treatment and 6 hours coronary reperfusion. Myocardial apoptosis was measured by TUNEL and the myocardial Bcl-2 and Bax protein expressions were assessed by immunohistochemistry. RESULTS: Compared with the IR group and the MI group, myocardial apoptosis was significantly reduced (P < 0.05) and the Bcl-2 protein expression increased (P < 0.01) while the Bax protein expression decreased (P < 0.05) in the RI-Post group. CONCLUSIONS: Remote renal postconditioning applied right before the onset of coronary artery reperfusion can reduce the myocardial apoptosis induced by myocardial ischemia and reperfusion and up-regulate Bcl-2 while down-regulate Bax expression possibly by activation of protein kinase C.

[Exploration on the relationship between thrombosis and stability of coronary atherosclerotic plaque in patients with unstable angina pectoris].

OBJECTIVE: To evaluate the correlation between thrombosis and stability of atherosclerotic plaque within criminal vessels in patients with unstable angina pectoris (UAP) by coronary angioscopy, to explore the clinical pathological basis for acute coronary syndromes (ACS). METHODS: Sixty-eight patients with UAP were enrolled, the patients with post-infarction angina pectoris and variant angina pectoris were excluded. There were 48 males and 20 females, aged from 40 to 73 (average 62.4 +/- 8.6) years. The criminal vessels of there patients were observed by coronary angioscopy during percutaneous coronary intervention (PCI) therapy. RESULTS: There were 68 criminal vessels in 68 patients. Atherosclerotic plaques were observed in all criminal vessels. Among criminal vessels, thrombi and intimae lesions were detected in 63 cases and 46 cases, respectively. Among 68 cases with atherosclerotic plaques, there were 48 cases of yellow plaques (70.5%), 18 cases of light yellow plaques (26.5%) and 2 cases of white plaques (2.94%). Sixty-three thrombi cases were mural and on-occlusive, which included 11 cases of red or mixed thrombi (17.5%) and 52 cases of white or pink thrombi (82.5%). All intimae lesions were accompanied by thrombosis, which included 11 cases of red or mixed thrombi (23.9%) and 35 cases of white or pink thrombi (76.1%). CONCLUSION: The study has shown that the rupture of unstable yellow plaque and its thrombosis were the pathological basis of UAP. Therefore, stabilizing yellow plaque before its rupture may play critical role in prevention and treatment of ACS.

[The diagnosis and therapy of chylous ascites].

OBJECTIVE: To discuss the diagnosis and therapy of chylous ascites. METHODS: To diagnose 40 patients of chylous ascite with regular test and quantitative analysis of chyle, direct lymphangiography, CT (immediately after direct lymphangiography), lymphangioscintigraphy, MRI. Twenty-two patients received conservative therapy, 18 patients received retroperitoneal lymphangiectomy and (or) lymph-vein shunting. RESULTS: Lymphatic dysplasia and chylous reflux were found in almost every patient, total parenteral nutrition showed good results. Followed up from 1 month to 5 years, in conservative therapy group, 9 patients were controlled well clinically, the condition of 6 patients was improved better. Seven patients showed no effect. In operation group, 11 patients were controlled well clinically. Four patients got mitigated. Total 7 patients died, although 4 of them ameliorated temporarily. CONCLUSIONS: Direct lymphangiography, CT (immediately after direct lymphangiography) are the most important diagnosis methods. The influence of the therapy to the malformed lymphatic system of patients should be well considered. Lymph-vein shunting, such as thoracic duct-left external jugular vein anastomosis, gastroenteral or retroperitoneal lymphatics-testicular or ovarian vein anastomosis, could improve the circulation of lymph and chyle of patients. Lymphatic microsurgery will play more and more important roles in the treatment of chylous diseases.