Hepatocyte growth factor modification enhances the anti-arrhythmic properties of human bone marrow-derived mesenchymal stem cells.

BACKGROUND/AIMS: Chronic myocardial infarction (MI) results in the formation of arrhythmogenic substrates, causing lethal ventricular arrhythmia (VA). We aimed to determine whether mesenchymal stem cells (MSCs) carrying a hepatocyte growth factor (HGF) gene modification (HGF-MSCs) decrease the levels of arrhythmogenic substrates and reduce the susceptibility to developing VA compared with unmodified MSCs and PBS in a swine infarction model. METHODS: The left descending anterior artery was balloon-occluded to establish an MI model. Four weeks later, the randomly grouped pigs were administered MSCs, PBS or HGF-MSCs via thoracotomy. After an additional four weeks, dynamic electrocardiography was performed to assess heart rate variability, and programmed electrical stimulation was conducted to evaluate the risk for VA. Then, the pigs were euthanized for morphometric, immunofluorescence and western blot analyses. RESULTS: The HGF-MSC group displayed the highest vessel density and Cx43 expression levels, and the lowest levels of apoptosis, and tyrosine hydroxylase (TH) and growth associated protein 43 (GAP43) expression. Moreover, the HGF-MSC group exhibited a decrease in the number of sympathetic nerve fibers, substantial decreases in the low frequency and the low-/high- frequency ratio and increases in the root mean square of successive differences (rMSSD) and the percentage of successive normal sinus R-R intervals longer than 50 ms (pNN50), compared with the other two groups. Finally, the HGF-MSC group displayed the lowest susceptibility to developing VA. CONCLUSION: HGF-MSCs displayed potent antiarrhythmic effects, reducing the risk for VA.

Cx43 in mesenchymal stem cells promotes angiogenesis of the infarcted heart independent of gap junctions.

Mesenchymal stem cells (MSCs) with elevated levels of connexin 43 (Cx43) have been shown to exhibit improved protection for ischemic hearts. However, it remains unclear whether Cx43 is involved in the paracrine actions of angiogenesis, the major mechanism of cell therapy. In the present study, an in vitro model with deprivation of oxygen and a murine myocardial infarction model with permanent ligation of the left anterior­descending (LAD) coronary artery were used to determine whether gap junctions in MSCs promote angiogenesis. It was observed that MSCs that overexpressed Cx43 (MSCs­Cx43), improve the cardiac function of infarcted myocardium as compared with control MSCs (MSCs­vector) and MSCs with Cx43 knocked down by small interfering RNA (MSCs­siCx43), accompanied with a reduction of infarct size and an increase in the vascular density and maturity. Increased levels of representative angiogenic factors [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)] were produced by MSCs­Cx43 compared with MSCs­siCx43 in vivo and in vitro. However, neither Cx43 formed gap junction specific inhibitor (Cx43 mimetic peptide) or gap junction opener (antiarrhythmic peptide) affected the production of VEGF and bFGF in MSCs under hypoxic stress. These data support the hypothesis that Cx43 in MSCs promotes angiogenesis in the infarcted heart, independent of gap junction formation.

[Catheter ablation of epicardial accessory pathway associated with coronary sinus musculature].

OBJECTIVE: To report the single-center clinical experience of catheter ablation of epicardial accessory pathway associated with coronary sinus musculature. METHODS: The data of 721 cases of left sided accessory pathway ablation were retrospectively analyzed. Ablation in the coronary sinus was performed in 17 (2.4 %) cases [11 males, mean age (37 ± 11) years]. RESULTS: Among the 17 cases, the accessory pathway was successfully ablated in middle cardiac vein and posterior lateral coronary sinus in 11 and 6 cases, respectively. Deverticulum of middle cardiac vein was seen in 2 cases. Mean time required to block the accessory pathway was (4.7 ± 2.7) s. An accessory pathway potential could be recorded at the target site in 10 out of 17 patients (59%). During a mean (21 ± 16) months follow up, only one patient experienced recurrence who was successfully cured by a second ablation session. No procedure related complication was reported. CONCLUSION: About 2.4% of left accessory pathway may have epicardial connection locating at middle cardiac vein or lateral part of the coronary sinus and require epicardial ablation. The epicardial ablation is safe and effective, warrants an excellent long-term results.

Association of CYBA rs7195830 polymorphism with estimated glomerular filtration rate in an adult Han sample from Jiangsu province, China.

BACKGROUND: Reactive oxygen species are thought to contribute to the development of renal damage. The P22phox subunit of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase, encoded by the cytochrome b245a polypeptide gene, CYBA, plays a key role in superoxide anion production. We investigated the association of CYBA rs7195830 polymorphism with estimated glomerular filtration rate (eGFR) and the role it plays in the pathogenesis of chronic kidney disease (CKD) in a Han Chinese sample. METHODS: The Gaoyou study enrolled 4473 participants. Serum levels of creatinine were measured and eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equations. The CYBA polymorphisms were genotyped. Then we investigated the association between eGFR and the rs7195830 polymorphism in the recessive model. RESULTS: The AA genotype of rs7195830 was associated with significantly lower values of eGFR compared with the GG and AG genotypes ((102.76 ± 17.07) ml×min(-1)×1.73 m(-2) vs. (105.08 ± 16.30) ml×min(-1)± 1.73 m(-2)). The association remained significant in the recessive model after adjusting for age, gender, body mass index, smoking, hypertension, diabetes mellitus, uric acid, triglyceride, low density lipoprotein cholesterol and high density lipoprotein cholesterol (ß=1.666, P=0.031). The rs7195832 AA genotype was an independent risk factor for CKD: eGFR <60 ml×min(-1)×1.73 m(-2) (odds ratio=3.32; 95% CI=1.21-9.13). CONCLUSION: The AA genotype of rs7195830 is independently associated with lower estimated glomerular filtration rate and is significantly associated with CKD.

[Clinical characteristics and genetic analysis of three pediatric patients with idiopathic restrictive cardiomyopathy].

OBJECTIVE: Restrictive cardiomyopathy (RCM) is rare in children, and little is known about the molecular basis of RCM. The aim of this study was to investigate the clinical and myopathological characteristics and to detect mutations on cardiac sarcomere protein genes in three idiopathic pediatric RCMs. METHODS: Detailed clinical characteristics and familiar history were obtained in three idiopathic pediatric RCMs. One hundred healthy pediatric individuals were recruited as controls. Histological evaluation was performed with heart tissue retrieved at catheterization in case-1 and case-2. The entire coding sequences of four cardiac sarcomere protein genes, including cardiac troponin T (TNNT2), cardiac troponin I(TNNI3), ß-myosin heavy chain (MYH7), and α-actin (ACTC)were screened for mutations. Sequence variants were then tested in the family as well as in 100 healthy control DNAs. RESULTS: All three index cases were diagnosed as primary RCMs without family history, and their clinical conditions deteriorated rapidly. Case-1 was in combination with ventricular septal defect. Case-2 was in combination with mid- and inferoseptal hypertrophy. In case-1, myocardial biopsies displayed extensive an isomorphism and disarray of cardiomyocytes; electron microscopy showed large stacks of severely dysmorphic megamitochondria and focal Z-disc streaming. In case-2, endomyocardial biopsy revealed moderate myocyte hypertrophy with mild interstitial fibrosis; transmission electron microscopy showed misalignment of Z-bands and unequal Z-Z band distances. Genetic analysis identified two heterozygous missense mutations in TNNI3, with R204H in case-1 and R192H in case-3 respectively. A de novo heterozygous deletion in TNNT2 (p. Asn100_Glu101del) was identified in case-2. Sequence analysis shows that all three mutations are located in a position highly conserved across many species. The three mutations were negative for their parents and controls. CONCLUSION: The clinical conditions in all three index cases are deteriorated rapidly after diagnosed as primary RCM. Three heterozygous mutations including two in TNNI3 and one in TNNT2 gene are identified in the three RCMs respectively, which are considered as causative mutations. These findings provide new insights into the molecular etiology responsible for pediatric RCM.

[Efficacy of catheter radiofrequency ablation for the treatment of ventricular arrhythmia storm post cardioverter-defibrillators implantation].

OBJECTIVE: To evaluate the acute and long-term effects of catheter radiofrequency ablation for the treatment of ventricular arrhythmia storm (VAS) post implantable cardioverter-defibrillators (ICD) implantation. METHODS: Acute and long-term effects of catheter radiofrequency ablation for the treatment of VAS post ICD implantation were retrospectively assessed in 11 patients from September 2008 to August 2011. RESULTS: A total of 15 ablation procedures were performed in 11 patients. Six ablation procedures were performed through epicardial approach. In 9 patients, 20 types of ventricular tachycardia (VT) (including 20% hemodynamically unstable VT) were induced during the procedures [mean cycle length (384 ± 141) ms] and polymorphic ventricular tachycardia were induced in 7 patients. The average X-ray fluoroscopy time and procedural time were (26 ± 17) min and (189 ± 60) min, respectively. Complete success, partial success, and failure rates immediately post catheter radiofrequency ablation were 46.7% (7/15), 26.7% (4/15) and 26.7% (4/15), respectively. All patients are alive at follow-up[(2.45 ± 9.6) months after the last catheter ablation] and the complete success, partial success, and failure rates during follow-up were 72.7% (8/11), 9.1% (1/11) and 18.2% (2/11), respectively. CONCLUSION: VAS can be effectively treated by catheter radiofrequency ablation in patients post ICD implantation.

Establishment and evaluation of a swine model of acute myocardial infarction and reperfusion-ventricular fibrillation-cardiac arrest using the interventional technique.

BACKGROUND: Ventricular fibrillation is the main cause of sudden cardiac death among patients with acute myocardial infarction (AMI). Substantial benefits could be obtained by both researchers and practitioners if an AMI reperfusion-ventricular fibrillation-cardiac arrest model were established. METHODS: Twenty swine were anesthetized and underwent occlusion of the left anterior descending branch for 90 minutes prior to blood reperfusion. Throughout this process, continuous 12-lead electrocardiography (ECG) was used to monitor heart rate, rhythm, and electrocardiogram alteration. Thereafter, AMI was confirmed by ECG and left ventricular angiography. Heart tissue was collected for pathological analysis, and for evaluation of the establishment of a model of AMI reperfusion. RESULTS: Seven swine died during the model establishment, and the 13 surviving swine were proven to have myocardial infarction; nine of those survivors had ventricular fibrillation-cardiac arrest after reperfusion based on the electrocardiograph and pathological examination. CONCLUSION: Blocking the left anterior descending branch by inflation of an over-the-wire coronary balloon catheter in swine can result in successful establishment of a swine model of AMI and reperfusion-ventricular fibrillation-cardiac arrest, with good reproducibility and a high survival rate.

[Initial experience of percutaneous coronary intervention guided by computed tomography coronary angiography derived roadmap and magnetic navigation system].

OBJECTIVE: To evaluate the feasibility, efficacy and safety of the percutaneous coronary intervention (PCI)guided by computed tomography (CT) coronary angiography derived roadmap and magnetic navigation system (MNS). METHODS: During June 2011 and May 2012, thirty consecutive patients receiving elective PCI were enrolled, coronary artery disease was primarily diagnosed by dual-source CT coronary angiography (DSCT-CA) at outpatient clinic and successively proved by coronary artery angiography in the hospital. Target vessels from pre-procedure DSCT-CA were transferred to the magnetic navigation system, and consequently edited, reconstructed, and projected onto the live fluoroscopic screen as roadmap. Parameters including characters of the target lesions, time, contrast volume, radiation dosage for guidewire crossing, and complications of the procedure were recorded. RESULTS: Thirty patients with 36 lesions were recruited and intervened by PCI. Among the target lesions, sixteen were classified as type A, 11 as type B1, 8 as type B2, 1 as type C. The average length of the target lesions was (22.0 ± 9.8) mm, and the average stenosis of the target lesions was (81.3 ± 10.3)%. Under the guidance of CT roadmap and MNS, 36 target lesions were crossed by the magnetic guidewires, with a lesion crossing ratio of 100%. The time of placement of the magnetic guidewires was 92.5 (56.6 - 131.3) seconds. The contrast volume and the radiation dosage for guidewire placement were 0.0 (0.0 - 3.0) ml and 235.0 (123.5 - 395.1) µGym(2)/36.5 (21.3 - 67.8) mGy, respectively. Guidewires were successfully placed in 21 (58.3%) lesions without contrast agent. All enrolled vessels were successfully treated, and there were no MNS associated complications. CONCLUSIONS: It is feasible, effective and safe to initiate PCI under the guidance of CT derived roadmap and MNS. This method might be helpful for the guidewire placement in the treatment of total occlusions.

Anticoagulation therapy in Chinese patients with non-valvular atrial fibrillation: a prospective, multi-center, randomized, controlled study.

BACKGROUND: Non-valvular atrial fibrillation is associated with an increased risk of ischemic stroke; however, the appropriate intensity of anticoagulation therapy for Chinese patients has not been determined. The purpose of this study was to compare the safety and the efficacy of standard-intensity warfarin therapy, low-intensity warfarin therapy, and aspirin therapy for the prevention of ischemic events in Chinese patients with non-valvular atrial fibrillation (NVAF). METHODS: A total of 786 patients from 75 Chinese hospitals were enrolled in this study and randomized into three therapy groups: standard-intensity warfarin (international normalized ratio (INR) 2.1 to 2.5) group, low-intensity warfarin (INR 1.6 to 2.0) group and aspirin (200 mg per day) group. All patients were evaluated by physicians at 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after randomization to obtain a patient questionnaire, physical examination and related laboratory tests. RESULTS: The annual event rates of ischemic stroke, transient ischemic attack (TIA) or systemic thromboembolism were 2.6%, 3.1% and 6.9% in the standard-intensity warfarin, low-intensity warfarin and aspirin groups, respectively (P = 0.027). Thromboembolic event rates in both warfarin groups were significantly lower than that in the aspirin group (P = 0.018, P = 0.044), and there was no significant difference between the two warfarin groups. Severe hemorrhagic events occurred in 15 patients, 7 (2.6%) in the standard-intensity warfarin group, 7 (2.4%) in the low-intensity warfarin group and 1 (0.4%) in the aspirin group. The severe hemorrhagic event rates in the warfarin groups were higher than that in the aspirin group, but the difference did not reach statistical significance (P = 0.101). The mild hemorrhagic and total hemorrhagic event rates in the warfarin groups (whether in the standard-intensity warfarin group or low-intensity warfarin group) were much higher than that in the aspirin group with the annual event rates of total hemorrhages of 10.2%, 7.6% and 2.2%, respectively, in the 3 groups (P = 0.001). Furthermore, there was no significant difference in all cause mortality among the three study groups. CONCLUSION: In Chinese patients with NVAF, the warfarin therapy (INR 1.6 - 2.5) for the prevention of thromboembolic events was superior to aspirin.

Testosterone is negatively associated with the severity of coronary atherosclerosis in men.

This study aimed to determine whether plasma testosterone is associated with the severity of coronary atherosclerosis in a group of 803 men who underwent elective coronary angiography. Testosterone levels were measured in 803 male patients who were categorized into three groups according to testosterone level tertiles. All patients underwent elective coronary angiography, and the severity of coronary artery disease (CAD) was determined by the Gensini score. Moreover, patients were classified into two groups according to Gensini scores (score ≤26 and score >26) using the median values as cutoff points. The plasma testosterone levels were measured by an ELISA kit. The level of testosterone was negatively associated with the Gensini score (r=-0.188; P=0.000). A multiple linear regression analysis revealed that testosterone was an independent risk factor for the Gensini score (ß=-0.110; P=0.002) after adjusting for confounding covariates. In a multivariate logistic regression model, the severity of CAD was shown to be significantly lower in the third tertile (highest) of testosterone compared to the first tertile (lowest) of testosterone (odds ratio (OR)=0.465; 95% confidence interval (CI): 0.327-0.662; P=0.000). In this study, patients with lower testosterone levels had higher Gensini scores in a group of 803 men who underwent elective coronary angiography. Additional studies are needed to clarify the direction of causality and possible underlying mechanisms.

Association of SNP rs6903956 on chromosome 6p24.1 with angiographical characteristics of coronary atherosclerosis in a Chinese population.

OBJECTIVE: To explore the association between rs6903956 and severity of coronary artery disease (CAD) in a Chinese population. METHODS: A cohort of 1075 consecutive patients who underwent coronary arteriography for suspected or known coronary atherosclerosis was enrolled in our study. Coronary atherosclerosis severity was defined by Gensini's Score System and counts of diseased vessels. RESULTS: Gensini score frequencies and counts of diseased vessels differed among GG, AG, AA genotype groups at the rs6903956 locus (p = 0.025 for Gensini score frequencies vs. p = 0.024 for counts of diseased vessels, respectively). A univariate logistic regression analysis revealed that the genotype distribution of this SNP was associated significantly with angiographical characteristics of coronary atherosclerosis risk (p = 0.030, odds ratio (OR) = 1.444, 95% confidence interval (CI) = 1.036∼2.013 for AG vs. GG; p = 0.021, OR = 5.896, 95% CI = 1.299∼26.750 for AA vs. GG and p = 0.007, OR = 1.564, 95% CI = 1.132∼2.162 for combined (AG+AA) vs. GG). A multivariate logistic regression analysis indicated that the genotype distribution of the rs6903956 polymorphism be associated significantly with the angiographical characteristics of coronary atherosclerosis risk (p = 0.004, OR = 1.578, 95% CI = 1.155∼2.154 for GG vs. AG vs. AA; p = 0.013, OR = 1.541, 95% CI = 1.097∼2.163 for GG vs. GA+ AA). A stratification analysis revealed that male subjects and smoking subjects had a higher frequency of the rs6903956 heterozygous mutant among higher Gensini score subjects than among lower Gensini score subjects (p = 0.023, OR = 1.579, 95% CI = 1.064∼2.344 for male subgroup; p = 0.005, OR = 2.075, 95% CI = 1.249∼3.448 for smoking subgroup). CONCLUSIONS: Allele A is a risk factor for CAD and the G-to-A allele substitution may underlie the association between rs6903956 and CAD.

Bradykinin ß2 receptor -58T/C gene polymorphism and essential hypertension: a meta-analysis.

BACKGROUND: Research has shown that bradykinin ß(2) receptor (BDKRB2) -58T/C gene polymorphism is correlated with the risk of essential hypertension (EH), but the results remain inconclusive. OBJECTIVE AND METHODS: The objective of this study was to explore the association between BDKRB2-58T/C gene polymorphism and EH. A meta-analysis of 11 studies with 3882 subjects was conducted. Pooled odds ratios (ORs) for the association between BDKRB2-58T/C gene polymorphism and EH and their corresponding 95% confidence intervals (CIs) were estimated using the random effects model. RESULTS: The BDKRB2-58T/C gene polymorphism was significantly correlated with EH under an allelic genetic model (OR = 1.24, 95% CI = 1.05-1.46; P = 0.01), a dominant genetic model (OR = 0.65, 95% CI = 0.47-0.90; P = 0.01), a recessive genetic model (OR = 1.146, 95% CI = 1.035-1.269; P = 0.009), a homozygote genetic model (OR = 1.134, 95% CI = 1.048-1.228; P = 0.002), and a heterozygote genetic model (OR = 1.060, 95% CI = 1.009-1.112; P = 0.019). CONCLUSIONS: The BDKRB2-58T/C gene polymorphism is associated with increased EH risk. The results of this study suggest that carriers of the -58C allele are susceptible to EH.

[Catheter ablation of focal atrial tachycardia:the topographic distribution and long-term outcome].

OBJECTIVE: To explore the topographic distribution and long-term outcome of catheter ablation for focal atrial tachycardia (AT). METHOD: The data of 207 patients who underwent electrophysiologic study for AT were retrospectively analyzed. RESULTS: A total of 200 AT were identified in 185 patients. The most common site for AT was ostium of the coronary sinus (23.8%), followed by crista terminalis (20.5%), perinodal area (20.0%), cava vena (17.8%), annulus (13.0%), and appendage (10.3%). Eighty percent AT originated from the right atrium, 17.8% originated from the left atrium. AT originated from the left atrium was more common in male than in female (25.0% vs. 13.3%, P = 0.042), while AT originated from the right atrium was more common in female than in male (69.4% vs. 86.7%, P = 0.004). Among the 185 patients, acute success ablation rate was 93.5% (n = 173). The acute success rate in the conventional mapping group was lower than that in the three-dimensional mapping group (79.3% vs. 96.5%, P < 0.01). During a median of 36 months follow up, the AT recurred in 20 patients (success ablation rate 88.4%). Success ablation rate was similar between the conventional mapping group and the three-dimensional mapping group (P > 0.05). CONCLUSIONS: Focal AT commonly originates from ostium of coronary sinus, crystal terminalis, perinodal area, and cava veins. There is a gender related difference in the distribution of focal AT. The radiofrequency catheter ablation yields a satisfying success rate and very low complication rate and could be the first line choice for treating ATs in experienced electrophysiological center.

Overexpression of FABP3 promotes apoptosis through inducing mitochondrial impairment in embryonic cancer cells.

Fatty acid-binding protein 3 (FABP3) is a low-molecular-weight protein with a distinct tissue distribution that may play an important role in fatty acid transport, cell growth, cellular signaling, and gene transcription. Previously, we have found that FABP3 was involved in apoptosis-associated congenital cardiac malformations, but the underlying mechanisms have not yet been described. In the present study, we investigated the characteristics of mitochondrial dysfunction in embryonic cancer cells (P19 cells) that overexpressed FABP3. We demonstrated that in FABP3-overexpressing P19 cells a lower cellular ATP production was accompanied by a dramatic decrease in mitochondrial membrane potential (MMP), despite the lack of a substantial decrease in the mtDNA copy number. In addition, FABP3 overexpression also led to an imbalance in mitochondrial dynamics and to excess intracellular reactive oxygen species production. Collectively, our results indicated that overexpression of FABP3 in P19 cells caused mitochondrion dysfunction that might be responsible for the development of FABP3-induced apoptosis.

Renin-angiotensin-aldosterone system gene polymorphisms and coronary artery disease: detection of gene-gene and gene-environment interactions.

OBJECTIVE: The objective of this study was to explore the association between coronary artery disease and genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) pathway. In addition, we examined the interactions between demographic and lifestyle risk factors (environmental factors including age, sex, smoking status, alcohol intake) and RAAS polymorphisms on disease risk. METHODS: A total of 1089 subjects who underwent coronary angiography were enrolled in this study. Eight RAAS polymorphisms were genotyped in this population: the G2350A (rs4343) polymorphism in exon 17 of the angiotensin converting enzyme (ACE) gene, 1166A→C (rs5186) and 573C/T (rs5182) in the angiotensin II type 1 receptor (AGTR1) gene, the -344C→T transversion (rs1799998) in the aldosterone synthase (CYP11B2) gene, and the G-217A (rs5049), G-6A (rs5051), M235T (rs699; T4072C), and T174M (rs4762; C3889T) polymorphisms in the angiotensinogen (AGT) gene. Subjects with coronary heart disease were defined as those with at least 50% stenosis in at least one major coronary artery, and, the severity of coronary atherosclerosis was defined by the Gensini scoring system. RESULTS: Compared to the subjects with AA genotype, the subjects with AG + GG genotype of rs1799998 had significant lower gensini score (p=0.029). After adjusting for age, gender, cigarette smoking, and alcohol intake status, the AG genotype (OR 0.717 95%CI 0.541-0.950, p=0.021) and the AG + GG genotype (OR 0.730 95%CI 0.559-0.954, p=0.021) distributions of rs1799998 were significantly different between the cases and controls compare to the AA genotype. Subjects with three at-risk loci had increased risk of coronary artery disease compared to subjects carrying 0 or 1 risk-associated polymorphism (OR [95% CI]:1.579 [1.077-2.316], p=0. 019), and the significance of the association was not reduced after adjusting for age, sex, cigarette smoking, or alcohol intake (adjusted OR [95% CI]: 1.673 [1.116-2.507], p=0.013). The results of multifactor-dimensionality reduction analysis revealed an interaction effect of CYP11B2 -344C→T, age, and smoking status on the risk of coronary heart disease (training OR [95% CI]: 3.7685 [2.8463-4.9895], p<0.0001; testing OR [95% CI]: 2.7583 [1.2038-6.3203], p=0.015). CONCLUSIONS: Subjects who carried the G allele of the rs1799998 polymorphism significantly associated with coronary heart disease and severity of coronary atherosclerosis estimated by the Gensini score in the whole population of the study. And, multiple RAAS gene polymorphisms are associated with coronary artery disease. The interaction of the CYP11B2 -344C→T polymorphism (rs1799998), age, and smoking status is also associated with enhanced risk of coronary artery disease.

Downregulation of quinone reductase 2 attenuates vascular smooth muscle cells proliferation and neointimal formation in balloon injured rat carotid artery.

BACKGROUND/AIMS: Quinone reductase 2 (NQO2) is a flavoprotein that catalyzes the metabolic reduction of quinines, but its biological mechanism in vascular smooth muscle cells (VSMCs) is unclear. The aim of this study was to evaluate the role of NQO2 on VSMCs proliferation and the neointimal formation in balloon injured rat carotid artery. METHODS: Left common carotid arteries from Sprague-Dawley rats were injured by a balloon catheter, and the injured arteries were incubated with 50 µL solution of NQO2-siRNA-GFP lentiviral vectors, NC-siRNA-GFP lentiviral vectors or PBS for 1 h. The rats were euthanized for morphometric and immunohistochemical analysis, real-time PCR and western blot analysis at 2 weeks after balloon injury and gene transfer. The cultured rat VSMCs transduced with NQO2-siRNA-GFP or NC-siRNA-GFP lentiviral vectors were used for cell proliferation assay, real-time PCR and western blot analysis. In order to detect the vascular or intracellular ROS level, the lentiviral vectors without GFP were used to transfect the injured common carotid arteries and the cultured rat VSMCs. RESULTS: Lentiviral vectors bearing NQO2 siRNA could reduce NQO2 protein level and suppress NQO2 mRNA expression in balloon injured artery walls and cultured rat VSMCs. Downregulation of NQO2 significantly suppressed VSMCs proliferation and intimal formation. NQO2 siRNA treatment could reduce vascular or intracellular ROS level and decrease the phosphorylation of the ERK1/2 in balloon injured artery walls and cultured rat VSMCs. CONCLUSION: Our study suggests that downregulation of NQO2 significantly suppresses VSMCs proliferation and progression of neointimal formation after vascular injury.

Risk factors and outcomes of post-procedure heart blocks after transcatheter device closure of perimembranous ventricular septal defect.

OBJECTIVES: The aim of this study was to analyze the risk factors and mid-term outcomes associated with post-procedure heart blocks (PPHBs) after transcatheter closure of perimembranous ventricular septal defect (pmVSD). BACKGROUND: The development of heart blocks remains a major challenge for transcatheter closure of pmVSD. METHODS: Transcatheter closure of pmVSD was carried out in 228 patients. Electrocardiography and 24-h Holter monitoring were performed before the procedure, within 1 week after the procedure, then 1, 3, 6, and 12 months, and every year thereafter. RESULTS: Thirty-three patients (14.5%) who received transcatheter closure of pmVSD developed PPHBs. PPHBs included right bundle branch block (57.6%), left bundle branch block (24.2%), and atrioventricular block (18.2%). High-degree atrioventricular blocks occurred in 4 patients and recovered to normal conduction after intravenous administration of hydrocortisone. PPHBs recovered to normal conduction in 21 patients by the time of hospital discharge. Compared with the patients without PPHBs, the patients suffering PPHBs were characterized by a significantly longer distance between the aortic valve and the defect (DAVD), a shorter distance from the lower rim of the defect to the septal leaflet of the tricuspid valve (DLRD-SLTV), and a larger diameter difference between the occluder and ventricular septal defect (DDOV). The earlier the PPHBs developed after the procedure, the more difficult the recovery to normal conduction. CONCLUSIONS: The outcome of PPHBs after transcatheter closure of pmVSD was satisfactory, as most patients recovered to normal conduction. Measurements of DLRD-SLTV, DAVD, and DDOV may be useful in predicting the incidence of PPHBs.

Time distribution of the onset of chest pain in subjects with acute ST-elevation myocardial infarction: an eight-year, single-center study in China.

OBJECTIVE: The objective of this study was to explore the time distribution patterns of the onset of chest pain in subjects with acute ST-elevation myocardial infarction in a Chinese population. METHODS: A total of 1467 patients with acute ST-elevation myocardial infarction were enrolled from 2003 to 2010. The hourly, daily, monthly, seasonal and day-of-week fluctuations in the prevalence of acute ST-elevation myocardial infarction were analyzed. RESULTS: A peak was found between the morning hours of 07:31 and 08:30. A second peak was observed between 14:31 and 15:30, and a third peak was found between 23:31 and 00:30 (p<0.001). The monthly maximum was recorded in November and the minimum was in April (p<0.001). The number of daily cases was greatest in autumn and lowest in the spring (p = 0.001). Day-of-the-week variations of ST-elevation acute myocardial infarction were not found, except in patients more than 75-years-old. CONCLUSIONS: Periodic variations in the frequency of ST-elevation acute myocardial infarction in Chinese patients showed significant differences with regard to diurnal, monthly and seasonal patterns. The exact mechanisms underlying these circadian variations require further study.

Expressing murine p56Hck(ca) promotes HeLa cells' motility and invasion via triggering redistribution of F-actin and microtubules.

Hck is the unique example among the Src PTKs to be expressed as two isoforms, which are generated by alternative translation. The two isoforms differs from each other by a 21 N-terminal amino acids sequence which supports myristoylation. Though it has been shown that these different acylation states govern the different subcellular localization of the isoforms and each Hck isoform could play a specific role, little study focus on the function of p56Hck. To investigated the role of p56Hck isoform in cell migration, GFP targeted p56Hck plasmid and its constitutively active form were constructed and transiently transfected into HeLa cells, F-actin staining and Indirect immunofluorescence for microtubules were then performed. Phagokinetic track motility assay and In vitro invasion assays were also investigated after transiently transfection respectively. In this study, we found ectopically expressing a constitutively active form of 56Hck will lead to membrane protrusion and F-actin reorganization in HeLa cells. Both 56Hck and its constitutive active form will lead to redistribution of microtubules and enhancement of cell motility and cell invasion. Hck inhibitor PP2 supplementation eliminated cell motility and cell invasion of p56Hck while PP3, a negative control of PP2 didn't eliminate cell motility and cell invasion of p56Hck. It is indicated that enhanced cell motility and cell invasion in p56Hck ectopically expressed HeLa cells are the results of reorganization of F-actin and microtubules.