Using machine learning to aid treatment decision and risk assessment for severe three-vessel coronary artery disease.

BACKGROUND: Three-vessel disease (TVD) with a SYNergy between PCI with TAXus and cardiac surgery (SYNTAX) score of ≥ 23 is one of the most severe types of coronary artery disease. We aimed to take advantage of machine learning to help in decision-making and prognostic evaluation in such patients. METHODS: We analyzed 3786 patients who had TVD with a SYNTAX score of ≥ 23, had no history of previous revascularization, and underwent either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) after enrollment. The patients were randomly assigned to a training group and testing group. The C4.5 decision tree algorithm was applied in the training group, and all-cause death after a median follow-up of 6.6 years was regarded as the class label. RESULTS: The decision tree algorithm selected age and left ventricular end-diastolic diameter (LVEDD) as splitting features and divided the patients into three subgroups: subgroup 1 (age of ≤ 67 years and LVEDD of ≤ 53 mm), subgroup 2 (age of ≤ 67 years and LVEDD of > 53 mm), and subgroup 3 (age of > 67 years). PCI conferred a patient survival benefit over CABG in subgroup 2. There was no significant difference in the risk of all-cause death between PCI and CABG in subgroup 1 and subgroup 3 in both the training data and testing data. Among the total study population, the multivariable analysis revealed significant differences in the risk of all-cause death among patients in three subgroups. CONCLUSIONS: The combination of age and LVEDD identified by machine learning can contribute to decision-making and risk assessment of death in patients with severe TVD. The present results suggest that PCI is a better choice for young patients with severe TVD characterized by left ventricular dilation.

Prognostic Values of Serum Chloride and Sodium Levels in Patients with Three-vessel Disease.

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION: Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.

Aortic Aneurysm in Takayasu Arteritis.

BACKGROUND: Aortic aneurysm (AA) is a severe complication of Takayasu arteritis (TA). This study aimed to evaluate the prevalence, clinical and imaging features, management and long-term outcomes of AA in patients with TA. MATERIALS AND METHODS: A retrospective study was performed of TA patients with AA admitted to Fuwai Hospital from 1996-2015. Baseline clinical data and follow-up data of TA patients with AA were collected and analyzed. RESULTS: Thirty-nine (4.2%) of 934 patients with TA were identified with AA that was related to vasculitis. The mean age at disease onset was 31 ± 10 years, with a female-to-male ratio of 1.79:1. The ascending aorta was the most common site of the aneurysmal lesion (18, 33.3%), and the most frequent manifestations associated with AA were chest tightness (12, 30.8%) and shortness of breath (12, 30.8%), which were usually concomitant with aortic valve insufficiency. Involvement of multiple sites in AA was found in 8 patients (20.5%), and multiple AAs were found in 5 patients (12.8%). No significant difference was observed in clinical and imaging findings between sexes. Of 25 patients (64.1%) with a median 72-month follow-up, 1 patient suffered from heart failure owing to perivalvular leakage, and 1 patient died, possibly related to severe complications of the operation. CONCLUSIONS: The prevalence of AA is relatively low in Chinese patients with TA. AA seems to develop more frequently in male patients with TA. Management should consider location and size of AA, complexity of vessel lesions and disease status. Long-term follow-up is indispensable.

A functional variant in the coding region of CAMTA2 is associated with left ventricular hypertrophy by affecting the activation of Nkx2.5-dependent transcription.

OBJECTIVE: The calmodulin-binding transcription activator 2 (CAMTA2) promotes transcription of genes involved in cardiac hypertrophy through its interaction with Nkx2.5 and is an indispensable transcription coactivator for cardiac hypertrophy. We hypothesized that variants in the coding region of CAMTA2 would affect its function and confer a risk of cardiac hypertrophy. METHODS: The effects of the variant rs238234 on the activity of the atrial natriuretic factor promoter and on the cardiomyocytes hypertrophy were assessed in the H9C2 cell line and primary neonatal rat cardiomyocytes, respectively. Furthermore, the association of this variant with left ventricular hypertrophy (LVH) was tested in hypertensive patients with and without hypertrophy (N = 325 and 697), and this analysis was replicated in an independent population of 987 hypertensive patients without hypertrophy and 463 hypertensive patients with hypertrophy. RESULTS: We found that the G allele of rs238234 activated the atrial natriuretic factor promoter more strongly than the C allele. The cell size of cardiomyocytes was larger in the presence of the Ad-CAMTA2 G allele, and the G allele was associated with significantly increased susceptibility to LVH in hypertensive [odds ratio (OR), 1.29; P = 0.009]. In the discovery cohort, after adjusting for age and sex, the GG genotype was significantly associated with increased LVH risk (OR, 1.75; P = 0.015). There was little attenuation of the ORs (1.62; P < 0.05) when adjusting for BMI, heart rate, blood pressure, smoking, and drinking and further adjusting all covariates including lipid levels and other major risk factors. However, the GC genotype did not show any association with LVH using three regressive models. Replication in the second study yielded similar results. CONCLUSION: Our results provide evidence that the rs238234 GG genotype in the coding region of CAMTA2 may increase the risk of LVH by affecting the activation of Nkx2.5-dependent transcription.

Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes. METHODS: A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C. RESULTS: Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers. CONCLUSIONS: Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.

Plasma concentrations of interleukin-6, C-reactive protein, tumor necrosis factor-α and matrix metalloproteinase-9 in aortic dissection.

BACKGROUND: The role of inflammation in aortic dissection (AD) has not fully been investigated. We evaluated the potential relationships between interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP-9) and AD. METHODS: Plasma concentrations of IL-6, TNF-α, MMP-9 and CRP were determined in 64 acute AD patients, 42 patients with chronic AD, 98 patients with hypertension alone, and 96 healthy subjects. RESULTS: IL-6 concentrations were higher in acute AD than that in hypertension and healthy controls (10.98±2.38 vs. 3.79±1.56 and 3.32±1.60 pg/ml, P<0.05, respectively). Increased CRP concentrations were found in acute AD compared with chronic AD and hypertension as well as healthy subjects (13.48±3.74 vs. 4.12±2.99, 1.62±0.65 and 1.12±0.35 mg/l, P<0.001, respectively). Higher MMP-9 concentrations were detected in acute AD, chronic AD and hypertension compared with healthy controls (37.75±9.38, 55.78±6.41 and 31.03±7.94 vs. 21.24±7.28 ng/ml, P<0.05, P<0.001 and P<0.05, respectively), and in the dead compared to the survived (107.29±9.38 vs. 86.80±7.93 ng/ml, P<0.001) among acute AD patients. In acute AD, the time after onset had positive correlation with TNF-α (r=0.497, P=0.000), and negative correlation with CRP (r=-0.424, P=0.000). Plasma CRP levels decreased significantly when the onset time increased (P=0.013). Moreover, in the patients with acute AD who underwent surgery and stenting, plasma MMP-9 concentrations increased immediately after surgical treatment and stenting, and reached the peak values at 24h, then decreased at 1 week (P<0.001). CONCLUSIONS: Our findings confirmed and extended previous studies that increased plasma inflammatory markers were significantly associated with AD.

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.

Recent molecular biological progress in Marfan syndrome and Marfan-associated disorders.

Marfan syndrome (MFS) is a connective tissue disorder with autosomal dominant inheritance. Advances in medicine and surgery have increased the average lifespan of classically affected patients. Serious visual and/or musculoskeletal impairment often has detrimental effects on day-to-day activities and quality of life. MFS patients suffer from many problems at younger ages and with higher frequencies than the general population because of the degenerative nature of the genetic condition. In classical MFS, changes are caused by mutations in the fibrillin-1 gene (FBN1). Mutations in the fibrillin-2 gene were discovered in individuals with a phenotypically related disorder, congenital contractural arachnodactyly. Some of the clinical manifestations of MFS cannot be explained by mechanical properties alone. Recently, mutations in the genes required for transforming growth factor-beta signaling (TGFBR1 and TGFBR2) have been found in several disorders with varying degrees of overlap with classical MFS, including Loeys-Dietz syndrome and familial thoracic aortic aneurysms and dissections. MFS is a disorder that is variable in its phenotypic expression. Specific information about mutations in the large FBN1 gene will give rise to more information about the phenotype-genotype correlations. Possible molecular mechanisms for the pathogenesis of MFS will be discussed which may assist healthcare professionals to control environmental factors that provoke individual complications in MFS.

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 microg/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.

The accelerated post-infarction progression of cardiac remodelling is associated with genetic changes in an untreated streptozotocin-induced diabetic rat model.

AIMS: The mechanism by which diabetes mellitus exacerbates myocardial injury and the incidence of heart failure after acute myocardial infarction (AMI), remains unclear. We studied the severity of cardiac dysfunction and time-dependent gene expression in a hyperglycaemic rat model with AMI. METHODS AND RESULTS: The diabetic model was produced by injection of streptozotocin in Sprague-Dawley rats. Ten weeks after induction of diabetes, AMI was induced by ligation of the left anterior descending coronary artery. Cardiac function and left ventricular (LV) dimensions were evaluated using two-dimensional echocardiography. Structural changes were assessed by histological examination. Gene expression profile was documented by using affymetrix genechip U230 2.0 array and real time-PCR. During 56 days post-AMI, lower survival rates, worse LV function, more severe fibrosis, and larger LV diameters were identified in diabetic rats compared with non-diabetic rats. A total 1221 genes involved in processes, such as glucose metabolism, fatty acid metabolism, extracellular matrix, and apoptosis, were found to be differentially expressed between diabetic and non-diabetic rats, of these 770 were up-regulated and 451 down-regulated. Up-regulation of the genes was found 1-2 weeks earlier in diabetic rats than in non-diabetic rats. CONCLUSION: The present data suggest that hyperglycaemia up-regulates remodelling-related genes, which may be responsible for the worse outcomes in diabetics than in non-diabetics after AMI.

Endothelium-specific overexpression of human IC53 downregulates endothelial nitric oxide synthase activity and elevates systolic blood pressure in mice.

AIMS: Hypertension is one of the major risk factors for cardiovascular diseases. Endothelial cells (ECs) exert important functions in the regulation of blood pressure. A novel gene, IC53, as an isoform of the cyclin-dependent kinase (CDK)-binding protein gene C53, is mainly expressed in vascular ECs and is upregulated in the failing heart of rats. Overexpression of IC53 promotes proliferation of ECs. To examine whether IC53 plays a role in the regulation of vascular tone and blood pressure, we constructed a transgenic (tg) mouse model of the IC53 gene and studied its phenotypes relevant to vascular function. METHODS AND RESULTS: IC53 cDNA was cloned from a human aorta cDNA library. Using the endothelium-specific VE-cadherin promoter, we constructed tg mice in which IC53 was specifically overexpressed in vascular endothelia and found that the tg mice exhibit elevated systolic blood pressure (SBP) in contrast to the wild-type (wt) controls. Further studies revealed impaired endothelium-dependent vasodilation, reduced nitric oxide (NO) production and decreased endothelial NO synthase (eNOS) expression, and activity in the tg mice. Inhibition of IC53 in human umbilical vein ECs induces upregulation of eNOS activity. CONCLUSION: Our results indicate that IC53 participates in the regulation of vascular homeostasis. Endothelium-specific overexpression of IC53 is associated with elevated SBP, which may be in part attributed to the downregulation of eNOS signalling.

[Prevalence and associated risk factors of hyperuricemia in rural hypertensive patients].

OBJECTIVE: To investigate the prevalence of hyperuricemia and its associated risk factors in treated and untreated hypertensive patients in Chinese rural area. METHODS: This cross-section study was performed in 5235 hypertensive patients aged 40 - 75 years old at Xinyang, Henan by using a multistage cluster sampling method. All patients underwent an investigation composed of a standardized questionnaire, physical and biochemical examination. Hyperuricemia was defined as serum uric acid levels > or = 420 micromol/L in men or > or = 360 micromol/L in women. RESULTS: The overall prevalence of hyperuricemia was 14.1%, and it was higher in men than in women (21.5% vs 10.2%, P < 0.01). With an increase of body mass index (BMI), the prevalence of hyperuricemia and serum uric acid level increased significantly in both sexes [BMI < 25, > or = 30: 14.4%, 30.4%, (328 +/- 83) micromol/L, (383 +/- 86) micromol/L in males; and 7.2%, 17.0%, (251 +/- 70) micromol/L, (293 +/- 75) micromol/L in females, respectively, all P < 0.01]. So did that with increase of age only in female patients (40 - 49 years vs > or = 70 years: 5.8% - 18.0%, respectively, P < 0.01). Antihypertensive treatment, lipid disorder, smoking and alcohol consumption also significantly increased the incidence of hyperuricemia and the serum uric acid level (all P < 0.01). However, no significant differences were found among patients with I, II, and III blood pressure levels (all P > 0.05). After adjustment for age and other conventional risk factors by using multiple logistic regression analysis, hyperuricemia was significantly associated with BMI, alcohol consumption and diuretics in males as well as BMI, lipid disorder, age, smoking, and antihypertensive treatment in females. CONCLUSIONS: Hyperuricemia is relatively less common in rural hypertensive patients. The associated risk factors of hyperuricemia and elevated serum uric acids include sex, age, BMI, antihypertensive medicines, lipid disorder, smoking and alcohol consumption. The effect of these factors is different between sexes.

[Outcome of patients with coronary artery disease underwent carotid artery stenting before coronary artery bypass surgery.].

OBJECTIVE: To evaluate the safety and efficacy of carotid artery stenting before open heart surgery. METHODS: Patients with heart disease and severe carotid artery stenosis received carotid stenting before open heart surgery were included in this prospective cohort study. The incidence of stroke, myocardial infarction and death from carotid stenting to 30 days after cardiac surgery was assessed. RESULTS: A total of 42 patients were enrolled. The carotid stenting procedural success rate was 100%. Distal embolic protection devices were used in 97.6% patients (41/42). Thirty-six (85.7%) patients received bypass surgery, 5 patients received bypass and valve replacement surgery (11.9%) and 1 patient received valve replacement surgery (2.4%) post carotid stenting. The incidence of stroke, myocardial infarction and death from carotid stenting to 30 days after cardiac surgery was 2.4% (1/42), 0% and 0% respectively. CONCLUSIONS: Our data from this small cohort study showed that carotid artery stenting before open heart surgery was safe and effective for patients with heart disease and severe carotid artery stenosis.

[The genotype-phenotype correlation of MYH7 gene G15391A mutation and MYBPC3 gene G12101A mutation in familial hypertrophic cardiomyopathy].

OBJECTIVE: To reveal genotype-phenotype correlation of disease-causing gene mutations in Chinese hypertrophic cardiomyopathy (HCM) pedigree. METHODS: Peripheral venous blood samples were collected from two Chinese HCM families and 120 healthy subjects were recruited as normal control. The full encoding exons and flanking sequences of the cardiac troponin T gene (TNNT2), beta-myosin heavy chain gene (MYH7) and myosin binding protein C gene (MYBPC3) were amplified with the polymerase chain reaction method, DNA sequencing was used to detect the mutation. RESULTS: In ZZJ family, mutation G12101A was identified in exon 21 of MYBPC3 gene in 4 family members [the arginine (R) converted to histidine (H)]. In this pedigree, three out of eight family members were diagnosed as HCM and with a penetrance of 75%. In FHL family, mutation G15391A was identified in exon 23 of MYH7 gene in 3 family members [the glutamic acid (E) converted to lysine (K)]. In this pedigree, three out of six family members were diagnosed as HCM and with a penetrance of 100%. Echocardiography showed obstruction of left ventricular outflow tract in two out of the three HCM patients. CONCLUSIONS: Our results showed that the G12101A mutation of MYBPC3 gene is the causal mutation of familial HCM with mild phenotype. The G15391A mutation of MYH7 gene is the causal mutation of familial HCM with malignant phenotype and a penetrance of 100%. Screening mutations in the MYH7 gene should be viewed as a reasonable procedure in obstructive HCM patients.

[Family hypertrophic cardiomyopathy caused by a 14035c > t mutation in cardiac troponin T gene].

OBJECTIVE: To study the disease-causing gene mutation in Chinese patients with familial hypertrophic cardiomyopathy (FHC) and to analyze the correlation between the genotype and the phenotype. METHODS: Peripheral blood samples were collected from 40 members from a family affected with FHC, and 120 healthy volunteers. PCR was performed to analyze the exons and flanking introns of the cardiac troponin T gene (TNNT2), beta-myosin heavy chain gene (MYH7), and myosin-binding protein C gene (MYBPC3) and the products were sequenced. The clinical data including symptom, physical examination, echocardiography and electrocardiography were collected. RESULTS: A 14035c > t mutation, which causes a missense mutation (R130C) in exon 10 of TNNT2 gene were identified in 4 family members, including the proband, female, aged 53, with the onset at the age of 30. The 4 persons with the 14035c > t mutation, all FHC patients, presented left ventricular dysfunction with a penetrance of 100%. Two of the patients died of sudden cardiac death during follow-up. No mutation was identified in the MYH7 and MYBPC3 genes. CONCLUSION: The 14035c > t mutation of TNNT2 gene is the causal mutation of FHC which is associated with malignant phenotype with a penetrance of 100%. It is a reasonable procedure in HCM patients with malignant phenotype to screen mutation in the TNNT2 gene.

Xuezhikang, an extract of cholestin, decreases plasma inflammatory markers and endothelin-1, improve exercise-induced ischemia and subjective feelings in patients with cardiac syndrome X.

Previous studies have demonstrated that Xuezhikang, an extract of cholestin, available from Chinese red yeast rice, could effectively modify lipid profile. The present study was undertaken to investigate whether Xuezhikang could modify endothelin-1 (ET-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (CRP) and exercise-induced ischemia in patients with cardiac syndrome X (CSX). Thirty-six patients with CSX were randomly assigned to 1200 mg/d of Xuezhikang or placebo group (n=18 respectively). Blood samples were drawn at day 0 and day 90 for measuring above parameters. The treadmill exercise tests and subjective feelings were also assessed at day 0 and day 90. The data showed that Xuezhikang therapy resulted in significant reductions in total cholesterol (TC, 19%), low-density lipoprotein cholesterol (LDL-C) (26%), and triglycerides (TG) compared with baseline (16%, p<0.01 respectively). The data also showed that Xuezhikang led significantly to reductions in median and log-CRP levels (38% and 44%, p<0.01 respectively), IL-6 (20%, p<0.01), and ET-1 (47%, p<0.01) compared with baseline. The exercise duration, and time to 1 mm ST-segment depression was significantly prolonged after Xuezhikang therapy (9% and 6%, p<0.05 respectively) accompanied by improvement of subjective feelings. Data suggested that the benefit of Xuezhikang resulted in significant modification vascular function by reduction of ET-1, inflammatory markers and LDL cholesterol, which may be clinically important for patients with CSX.

[Electrophysiological characterization of long QT syndrome associated mutations V630A and N633S].

OBJECTIVE: To identify the electrophysiological properties of long-QT syndrome (LQTS) associated missense mutations in the outer mouth of the HERG potassium channel in vitro. METHODS: Mutations V630A and N633S were constructed by Megaprimer PCR method and cRNA were produced by T7 RNA polymerase. The electrophysiological properties of the mutation were investigated in the Xenopus oocyte heterologous expression system. RESULTS: Coexpression of mutant and wild-type HERG subunits caused a dominant-negative effect, and the currents were significantly decreased. Compared with wild-type HERG channels, V630A and N633S mutations were related to decreased time constants for inactivation for V630A/WT and N633S/WT at all potentials, reduced slope conductance and the voltage dependence of steady-state inactivation was shifted to negative potentials for V630A/WT and N633S/WT. CONCLUSION: Present study shows that LQTS associated missense mutations located in the outer mouth of HERG cause a dominant-negative effect and alterations in steady-state voltage dependence of channel gating of heteromultimeric channels suggesting a reduction in expressional current might be one of the pathophysiologic mechanisms of LQTS.

[A novel LMNA gene mutation E82K associated with familial dilated cardiomyopathy].

OBJECTIVE: To examine the function of the novel mutation E82K in LMNA gene identified in a Chinese family infected by dilated cardiomyopathy. METHODS: (1) One Chinese family infected by dilated cardiomyopathy was chosen for the study. Exons 1-12 of the LMNA gene were screened with both PCR method and the cycle sequencing of the PCR products. (2) cDNA of the E82K mutation or wild type of LMNA gene was transfected into HEK293 cells and the apoptosis of the cells was detected after treatment with 0.8 mmol/L H2O2. RESULTS: (1) A new mutation E82K in LMNA gene was identified in this dilated cardiomyopathy family. (2) Apoptosis was more in the HEK293 cells transfected with E82K mutation than those with empty vector or wild type LMNA gene. CONCLUSIONS: The missense mutation E82K in LMNA gene changed the polar of the amino acid. It showed a malignant phenotype of severe clinical symptoms, early onset, poor survival prognosis and might be associated with atrioventricular conduction block (II degrees-III degrees), suggesting that the E82K mutation in LMNA gene may be a candidate for nosogenesis of dilated cardiomyopathy.

[Clinical results of stent revascularization as treatment for renal artery stenosis during 6 months of follow-up].

OBJECTIVES: To evaluate the safety and midterm efficacy of stent revascularization as treatment for renal artery stenosis. METHODS: Percutaneous transluminal renal angioplasty with stent (PTRA) was performed because of poorly controlled hypertension or preservation of renal function in 150 consecutive patients with severe renal artery stenosis, caused by atheroma (96 patients), arteritis (44 patients) and fibromuscular dysplasia (10 patients). All of them subsequently underwent 6-month clinical follow-up to observe the effect of the procedure on renal function, blood pressure control, number of antihypertensive medications. RESULT: Angiographic success was obtained in 148 (98.7%) of 150 patients after PTRA. At 6 months, both systolic and diastolic blood pressures significantly decreased (from 169.6 to 142.7 mm Hg and from 97.3 to 83.3 mm Hg, respectively; P < 0.001), and less antihypertensive medication was taken (from 2.7 to 1.9). The blood pressure became normal without taking any antihypertensive medications in 48 of 150 patients (32.0%), and the blood pressure control was more facile in 78 patients (52.0%), however, there were no improvement in 22 patients (16.0%). Creatinine level decreased in 34 patients (22.7%), remained stable in 112 patients (74.6%), and increased in 4 (2.7%). There was no statistical significance. No deaths occurred during 6-months follow-up. CONCLUSIONS: Renal artery stent revascularization had a beneficial effect on blood pressure control and a nondeleterious effect on renal function during 6-months follow-up. The long-term efficacy should be investigated. The procedure is safe in usual.

Time course of inflammatory response after renal artery stenting in patients with atherosclerotic renal stenosis.

BACKGROUND: Inflammatory response has been demonstrated in patients with coronary artery disease after percutaneous coronary intervention (PCI). Such response following renal artery stenting has not yet been established, however, in patients with atherosclerotic renal artery stenosis. METHODS: A total of 44 patients were enrolled in this study. Of them, 22 patients with atherosclerotic renal artery stenosis received renal angioplasty with stent (group A, mean age 51+/-8 years), and 22 patients with age- and gender-matched underwent renal angiography for diagnostic purpose as a control group (group B, age 50+/-8 years). The peripheral blood samples were taken immediately before the procedure, 1, 6 and 24 h after the procedure in both groups. The concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) were measured using ELISA. RESULTS: The result showed that there was no difference in clinical characteristics and baseline levels of CRP and IL-6 between the groups. The IL-6 increased in the first hour (before: 5.8+/-3 pg/ml; 1 h: 8.6+/-5 pg/ml, p<0.01), lasted at 6 h (12.2+/-8 pg/ml), returned to baseline at 24 h (5.4+/-3 pg/ml) in group A. The CRP did not changed at the first hour after stenting, but mean CRP increased from 0.30+/-0.09 to 0.37+/-0.15 mg/dl at 6 h (p<0.05), and peaked at 24 h (0.43+/-0.18 mg/dl, p<0.001 compared with baseline and control) after stenting in group A, while no such changes were observed in group B (p>0.05 at different time points compared with baseline and group B, respectively). CONCLUSIONS: The data indicated that renal artery stenting could trigger inflammatory response by evidence of increased plasma levels of CRP and IL-6. IL-6, however, was an early initiator of inflammatory cytokine, and CRP was a later marker of systemic inflammatory response to renal artery stenting.