Synergistic Effect of Lipoprotein-Associated Phospholipase A2 with Classical Risk Factors on Coronary Heart Disease: A Multi-Ethnic Study in China.

AIMS: We evaluated the synergistic effect of lipoprotein-associated phospholipase A2 (Lp-PLA2) in association with classical risk factors in predicting coronary heart disease (CHD) and demonstrated the diagnostic value of Lp-PLA2 for predicting coronary stenotic lesions in subjects with CHD. METHODS: Blood samples were acquired from 911 consecutive adult subjects (662 males and 249 females) from 11 ethnic groups. Lp-PLA2 plasma levels were detected using a commercially available turbidimetric immunoassay (TIA). CHD in patients was confirmed using coronary angiography, and the severity of coronary atherosclerosis was assessed using the Gensini scoring system. RESULTS: A binary logistic regression was performed to analyse the relationships between Lp-PLA2 and other risk factors. A multivariate logistic regression analysis revealed that Lp-PLA2 levels were significantly associated with CHD (OR, 1.882; 95% CI, 1.369-2.587, p=0.000).The area under the receiver operating characteristic curve for Lp-PLA2 was 0.589 (95%CI, 0.549-0.629, p=0.000).The synergism between Lp-PLA2 and other risk factors was also investigated. The proportion of CHD attributable to the interaction between Lp-PLA2 and age was as high as 64%. CONCLUSIONS: Lp-PLA2 levels in human plasma were positively associated with the severity of CHD, and there was a clear positive interaction between Lp-PLA2 and classical risk factors in predicting CHD.

Relationship between diagonal earlobe creases and coronary artery disease as determined via angiography.

OBJECTIVE: This study was designed to examine the prevalence of unilateral and bilateral diagonal earlobe creases (DELCs) with respect to the diagnosis of coronary heart disease (CHD). METHODS: A total of 558 consecutive participants (402 males and 156 females) aged 36-91 years who underwent coronary angiography were enrolled in this study. The participants were classified as being without a DELC, having a unilateral DELC and having bilateral DELCs; participants with either a unilateral DELC or bilateral DELCs were defined as participants with DELCs. Significant CHD was defined as at least one major vessel with >50% stenosis, and coronary atherosclerosis severity was defined using the Gensini scoring system. RESULTS: In the present study, bilateral DELCs were more frequently among male (p=0.001), CHD (p=0.000), older people (p=0.000) and those with more severe coronary artery atherosclerosis (p=0.000). The results of the multiple regression analyses indicated that DELCs (OR, 4.861; 95% CI 3.093 to 7.642, p=0.000) remained independently associated with a risk of CHD. It was assumed that participants without a DELC have a certain background risk for CHD (OR is assumed to be 1); the results of the multivariate logistic regression indicated that the relative risk of CHD among participants with bilateral DELCs was 5.690 among all participants (OR, 5.690; 95% CI 3.450 to 9.384, p=0.000), 5.436 among male participants (OR, 5.436; 95% CI 2.808 to 10.523, p=0.000) and 7.148 among female participants (OR, 7.148; 95% CI 3.184 to 16.049, p=0.000). Moreover, a positive association between DELC and age (SI=1.21, SIM=1.65, AP =0.132), gender (SI=2.09, SIM=0.81, AP=0.49) and smoking status (SI=1.49, SIM=0.73, AP=0.29) was found, respectively. CONCLUSIONS: The results of the present study indicated that DELCs are a simple and a feasible means of identifying CHD. However, the exact mechanism underlying the relationship between DELCs and CHD warrants further study.

Interaction between microRNA expression and classical risk factors in the risk of coronary heart disease.

The aim of this study was to identify the synergistic effect of microRNA expression with classical risk factors of coronary heart disease (CHD) and to explore their diagnostic value for coronary stenotic lesions in subjects with CHD. Plasma samples were obtained from 66 subjects with CHD and from 58 control individuals. A quantitative reverse-transcription PCR (RT-qPCR) assay was conducted to confirm the relative expressions of the known CHD-related miRNAs. The severity of coronary atherosclerosis was based on the Gensini scoring system. The expression of miR-125b in plasma of the CHD group was lower than that of the non-CHD group (0.14 ± 0.09 vs. 0.18 ± 0.10, p = 0.055), and the miR-125b levels significantly decreased following an increasing Gensini score (P = 0.037). Spearman correlation analyses indicated the Gensini score was negatively associated with miR-125b (r = -0.215, p = 0.017). Of all the miRNAs, miR-125b showed the lowest AUC (0.405; 95% CI: 0.305 ~ 0.506, p = 0.070). We found several synergistic effects between miR-125b and classical risk factors, such as age, sex, CR, FBG and HDL-C; the proportion of CHD attributable to the interaction of miR-125b and age was as high as 80%. Therefore, miR-125b was shown to play an important role in individual's susceptibility to developing CHD.

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

OBJECTIVE: The purpose of this study was to investigate the influence of weather on the occurrence of acute ST-elevation myocardial infarction in Chinese subjects. METHODS: Weather and climate data, as well as the occurrence of STEMI, were monitored at 2 am, 8 am, 2 pm, and 8 pm between 2003 and 2010. Generalized additive Poisson models were utilized to plot the numbers of patients with STEMI within 6 hour intervals against climatological variations, after accounting for the effects of the hour and season. RESULTS: The inclusion of meteorological conditions, including observed atmospheric pressure (hPa, hectopascal) variations during the previous three hours and temperature (°C, degrees Celsius), significantly affected the occurrence of STEMI, as measured every six hours. Compared with the 50th percentile of atmospheric pressure variations, the RRs (95% CI) for the first percentile, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and 99th percentile of atmospheric pressure variation over lag 0 were 1.66 (1.36∼2.03), 1.47 (1.30∼1.67), 1.22 (1.12∼1.33), 1.16 (1.07∼1.25), 1.27 (1.13∼1.43), and 1.16 (0.92∼1.46), respectively. Compared to the 50th percentile of temperature, the RRs (95% CI) for the first percentile, 10th percentile, 25th percentile, 75th percentile, 90th percentile, and 99th percentile of temperature over lag 0 were 0.58 (0.40∼0.83), 0.60 (0.46∼0.78), 0.69 (0.57∼0.83), 1.33 (1.14∼1.56), 1.39 (1.13∼1.71), and 1.17 (0.84∼1.63), respectively. CONCLUSIONS: Based on the eight-year, single-center study, significant relationships were observed among the occurrence of STEMI and atmospheric pressure variations during the previous three hours and temperature after account for long-term time trends.

Combined effects of admission serum creatinine concentration with age and gender on the prognostic significance of subjects with acute ST-elevation myocardial infarction in China.

OBJECTIVE: to explore the impact of admission serum creatinine concentration on the in-hospital mortality and its interaction with age and gender in patients with acute ST-segment elevation myocardial infarction (STEMI) in China. METHODS: 1424 acute STEMI patients were enrolled in the study. Anthropometric and laboratory measurements were collected from every patient. A Cox proportional hazards regression model was used to determine the relationships between the admission serum creatinine level (Cr level), age, sex and the in-hospital mortality. A crossover analysis and a stratified analysis were used to determine the combined impact of Cr levels with age and gender. RESULTS: Female (HR 1.687, 95%CI 1.051 ∼ 2.708), elevated Cr level (HR 5.922, 95%CI 3.780 ∼ 9,279) and old age (1.692, 95%CI 1.402 ∼ 2.403) were associated with a high risk of death respectively. After adjusting for other confounders, the renal dysfunction was still independently associated with a higher risk of death (HR 2.48, 95% CI 1.32 ∼ 4.63), while female gender (HR 1.19, 95%CI 0.62 ∼ 2.29) and old age (HR 1.77, 95%CI 0.92 ∼ 3.37) was not. In addition, crossover analysis revealed synergistic effects between elevated Cr level and female gender (SI = 3.01, SIM = 2.10, AP = 0.55). Stratified analysis showed that the impact of renal dysfunction on in-hospital mortality was more pronounced in patients <60 years old (odds ratios 11.10, 95% CI 3.72 to 33.14) compared with patients 60 to 74 years old (odds ratios 5.18, 95% CI 2.48 ∼ 10.83) and patients ≥ 75 years old (odds ratios 3.99, 95% CI 1.89 to 8.42). CONCLUSION: Serum Cr concentration on admission was a strong predictor for in-hospital mortality among Chinese acute STEMI patients especially in the young and the female.

Hemoglobin A1c risk score for the prediction of coronary artery disease in subjects with angiographically diagnosed coronary atherosclerosis.

OBJECTIVE: To develop a risk score by incorporating Hemoglobin A1c(HbA1c) with traditional risk factors for the prediction of coronary artery disease (CAD) in Chinese subjects. METHODS: A total of 196 consecutive subjects (131 males and 65 females) aged 38-89 years who underwent coronary angiography were enrolled in this study. HbA1c risk score sheets for the prediction of CAD were developed using age, gender and HbA1c. A receiver-operating characteristic curve analysis was used to determine the optimum cut-off levels of the HbA1c risk score for predicting CAD. RESULTS: In the ROC curve analysis, the optimal cut-off value of the HbA1c score for predicting CAD was 5.1, with a sensitivity of 72.0% and a specificity of 75.5% (area under the curve 0.781, 95% confidence interval 0.709 to 0.854, p=0.000). CONCLUSIONS: The HbA1c score system is a simple and feasible method that can be used for the prediction of CAD. Large-scale studies are needed to further substantiate these results.

Relationship of renin-angiotensin-aldosterone system polymorphisms and phenotypes to mortality in Chinese coronary atherosclerosis patients.

We performed a large, long-term cohort study to evaluate the association of renin-angiotensin-aldosterone system gene polymorphisms and baseline phenotypes to all-cause mortality among patients with angiographically confirmed coronary atherosclerosis. The study included 1075 subjects who underwent coronary angiography. Patients were genotyped for eight polymorphisms (rs4343, rs5186, rs5182, rs5049, rs5051, rs699, rs4762, and rs1799998), and their baseline plasma angiotensin II and aldosterone levels were measured. The interval between baseline and follow-up time-points ranged from 6.39 to 9.59 years. The results of multivariate regression analysis further indicated that high baseline angiotensin II levels (1.226 (1.024-1.468), p = 0.027) were independently associated with all-cause death. Therefore, we found that an increased baseline plasma angiotensin II level was associated with higher long-term all-cause mortality, even after correcting for established cardiovascular risk factors.

A correlation between acute kidney injury and myonecrosis after scheduled percutaneous coronary intervention.

Slight elevations in cardiac troponin I and T are frequently observed after percutaneous coronary intervention (PCI). Contrast-induced acute kidney injury (CI-AKI) is a complex syndrome induced by exposure to intravascular contrast media (CM). Currently, the relationships between the CM, pre-existing kidney insufficiency, CI-AKI, and myonecrosis after elective PCI are unclear. To investigate the relationship between CI-AKI and post-procedural myonecrosis (PMN) after PCI, we analyzed 327 non-ST-segment elevation acute coronary syndrome subjects undertaking elective PCI. The levels of cardiac troponins (cTns), cTnI and cTnT, at baseline and on at least one occasion 18-24 h after PCI were measured. We also recorded serum levels of creatinine (SCr) and the urine albumin:creatinine ratio (ACR) before coronary angiography, and 24-48 h and 48-72 h after contrast administration. A post-procedure increase in cTns was detected in 16.21% (53/327) of subjects with cTns levels >99th to 5×99th percentile upper reference limit (URL). Twenty-seven patients (8.26%) developed CI-AKI. CI-AKI occurred more often in subjects with PMN than in those without PMN (20.8% versus 5.8%, respectively, P=0.001). Multiple logistic regression analysis revealed that pre-existing microalbuminuria (MA) was an important independent predictor of PMN (OR: 3.31; 95% CI: 1.26-8.65, P=0.01). However, there was no correlation between the incidence of CI-AKI and PMN (OR: 2.38; 95% CI: 0.88-6.46, P=0.09). We conclude that pre-existing MA was not only an important independent predictor of CI-AKI but also of PMN.

[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.

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.

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.

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.

Negative association between free triiodothyronine level and international normalized ratio in euthyroid subjects with acute myocardial infarction.

AIM: To investigate the relationship between free triiodothyronine (FT3) and the international normalized ratio (the ratio of the prothrombin time of a patient to the normal sample, INR) in Chinese euthyroid subjects with acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 231 consecutive patients (177 males, 54 females) with STEMI were enrolled. Anthropometric and laboratory measurements, including heart rate, respiratory rate, blood pressure, body temperature, platelet count, INR, prothrombin time, activated partial thromboplastin time, FT3, free thyroxine (FT4), and thyroid-stimulating hormone, were collected from all the patients. The levels of FT3 and FT4 were measured with a full-automatic immune analyzer. The INR was determined using a coagulation analyzer. RESULTS: Patients were classified into 4 groups according to their quartile FT3 and FT4 levels: 0.40-3.09 (n=52), 3.10-3.69 (n=56), 3.70-4.29 (n=64) and 4.30-7.10 (n=59) for FT3; 4.9-14.8 (n=57), 14.9-16.8 (n=58), 16.9-18.7 (n=57) and 18.8-29.0 (n=59) for FT4. Subjects with a high FT3 level had significantly lower values of INR than those with a low FT3 level (P=0.01). Multiple linear regression analysis revealed decreased serum FT3 as an independent risk factor for elevated INR values (ß=-0.139, P=0.025). The value of INR was similar among the 4 groups according to the quartile FT4 levels (P=0.36). CONCLUSION: Free triiodothyronine was negatively associated with INR in the patients with acute STEMI and normal thyroid function.

[Activation of calcium-sensing receptors is associated with apoptosis in cardiomyocytes under simulated ischemia/reperfusion].

OBJECTIVE: To examine the association of activation of calcium-sensing receptors (CaSR) with apoptosis in cardiomyocytes under simulated ischemia/reperfusion. METHODS: Ventricular cardiomyocytes of neonatal rats were incubated in ischemia-mimetic solution for 2 h, then re-incubated in normal culture medium for 24 h to establish a model of simulated ischemia/reperfusion (I/R). Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay). The expression of CaSR mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of Caspase -3 and Bcl-2 was detected by Western blotting. RESULT: The simulated I/R enhanced the expression of CaSR and cardiomyocyte apoptosis. GdCl(3), a specific activator of CaSR, further increased the expression of CaSR and cardiomyocyte apoptosis, along with upregulation of Caspase-3 and downregulation of Bcl-2. CONCLUSION: CaSR is associated with I/R injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting Caspase -3 expression.

Severity of coronary atherosclerosis is an independent predictor of the left ventricular ejection fraction.

1. We studied the association between the level of the left ventricular ejection fraction and the severity of coronary atherosclerosis. 2. The study population consisted of 850 consecutive patients who underwent coronary angiography for suspected or known coronary atherosclerosis. Anthropometric measurements including the body mass index, blood pressure, blood lipids, blood glucose and leucocyte count were taken. The severity of coronary atherosclerosis was defined by the Gensini score. 3. When the level of the left ventricular ejection fraction was examined as a categorical variable classified by quartile values, subjects with a high left ventricular ejection fraction level had significantly lower Gensini scores than those with a low left ventricular ejection fraction level (P=0.000). Spearman's correlation analysis suggested that the left ventricular ejection fraction was significantly negatively associated with Gensini score (r= -0.213, P=0.000). Multiple stepwise linear regression analysis showed that the Gensini score was significantly independently associated with the left ventricular ejection fraction level (ß= -0.194, P=0.000). Furthermore, multivariable stepwise logistic regression analysis showed that the Gensini score was the independent risk factor for dysfunction of left ventricular ejection (OR=2.048, 95% CI=1.517-2.763). 4. The severity of coronary atherosclerosis was defined by the Gensini score. This was a strong and statistically highly significant predictor of the left ventricular ejection fraction level and dysfunction of left ventricular ejection independent of other major risk factors including age, body mass index, blood pressure, fasting blood glucose, blood lipid and leucocyte count.

Inhibitory effect of hepatocyte growth factor on cardiomyocytes apoptosis is partly related to reduced calcium sensing receptor expression during a model of simulated ischemia/reperfusion.

Calcium-sensing receptors (CaSR) are G-protein coupled receptors which maintain systemic calcium haemeostasis, participate in hormone secretion, activation of iron channel, cell apoptosis, proliferation and differentiation. Previous studies have show CaSR induce apoptosis in isolated rat adult heart and in normal rat neonatal cardiomyocytes by G-protein-PLC-IP3 signaling transinduction. A few of studies had demonstrated that CaSR induce apoptosis in cultured neonatal rat cardiomyocytes during ischemia/reperfusion. Hepatocyte growth factor (HGF), as a mesenchymally derived heterodimeric glycoprotein, play vital role in mitogenesis, angiogenesis, cellular motility and growth and anti-apoptosis after postinfarction heart failure via activation of transmembrane tyrosine kinase cell surface receptor c-Met. However, little knowledge exists about whether anti-apoptotic role of HGF in preventing cardiomyocytes injury induced by ischemia/reperfusion is associated with downregulation of CaSR expression. We incubated primary neonatal rat ventricular cardiomyocytes in ischemia-mimetic solution for 2 h, then reincubated them in normal culture medium for 24 h to establish a model of simulated ischemia/reperfusion (I/R). Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. The expression of CaSR mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, we analyzed the expression of Caspase-3, Bcl-2 and Phosphoinositide 3-kinase (PI3K) by Western blotting. The simulated I/R enhances the expression of CaSR and cardiomyocyte apoptosis. GdCl3, a specific activator of CaSR, further increase the expression of CaSR and Cardiomyocyte apoptosis, along with upregulation of Caspase-3, downregulation of Bcl-2 and inhibiting PI3K phosphorylation. Combination of GdCl3 with LY294002 (a selective PI3K inhibitor) increased Cardiomyocytes apoptosis but did not increased CaSR expression. Treatment of HGF decreased I/R- and GdCl3-induced apoptosis by suppressing Caspase-3 and promoting Bcl-2 and PI3K phosphorylation expression in accordance with downregulation of CaSR expression. HGF exerts protective role in I/R-induced apoptosis at least in part by inhibiting CaSR expression along with promoting Bcl-2, suppressing Caspase-3 expression and stimulating PI3K phosphorylation signaling pathway.

[Clinical study on the coronary artery interventions guided by the magnetic navigation system].

OBJECTIVE: To investigate the efficacy and safety of the magnetic navigation system used in the real world percutaneous coronary artery intervention. METHODS: All lesions detected by the coronary artery angiography in the magnetic-navigation catheter lab indicated for percutaneous coronary artery intervention (PCI) were included and treated under the guidance of the magnetic navigation system. The characteristics of the target lesion, process of the procedure, time and dosage of the X-ray exposure, and procedure-related complication were recorded and analyzed. RESULTS: One hundred and twenty one patients with 138 lesions were recruited and intervened by PCI during the period from April 2006 to June 2008. Thirty lesions were classified as type A, 50 as type B1, 36 as type B2, 22 as type C (including seven total occlusions). The average stenosis of the target lesions was (85.3 +/- 10.0)%, mean length was (21.1 +/- 10.0) mm. Under the guidance of the magnetic navigation system, 134 target lesions were passed by the magnetic guide-wires, the lesion passing ratio was 97.1%. The X-ray exposure time, X-ray dosage and the contrast volume used during the period of the wire placement were (55.9 +/- 35.4) seconds, (98.0 +/- 86.1) mGy/(490.0 +/- 422.2) microGym(2) and (8.0 +/- 5.4) ml, respectively. A total of 164 stents were implanted in the vessels where the target lesions were passed by the magnetic wires. There was no magnetic navigation system associated complication. Magnetic guide-wires failed to pass four target lesions, two of which were chronic total occlusions (CTOs), and the other two were calcified subtotal occlusions. CONCLUSIONS: It is feasible and safe to adopt the magnetic navigation system for the real-world coronary artery intervention. The magnetic guide-wire possesses a high lesion-passing ratio. The CTOs and calcified subtotal occlusions are not ideal lesions for use of the magnetic navigation system.

[Hepatocyte growth factor attenuates ischemia/reperfusion induced cardiomyocyte apoptosis via downregulating calcium sensing receptor expression].

OBJECTIVE: To examine whether the anti-apoptotic effect of hepatocyte growth factor (HGF) in cardiomyocytes underwent ischemia/reperfusion (I/R) is associated with downregulation of calcium sensing receptor (CaSR) mRNA expression. METHODS: Neonatal rat cardiomyocytes were isolated and randomly divided into 7 groups: control, I/R, GdCl(3), GdCl(3) + NiCl(2) + CdCl(2), GdCl(3) + LY294002, GdCl(3) + HGF, GdCl(3) + HGF + LY294002.I/R was established by incubating primary neonatal rat ventricular cardiomyocytes in ischemia-mimetic solution for 2 h, then reincubated in normal culture medium for 24 h. Cardiomyocyte apoptosis was detected by TUNEL. The expression of CaSR mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of Caspase-3, Bcl-2 and Phosphoinositide-3 Kinase (PI3K) was analyzed by Western blot. RESULTS: I/R enhanced the expression of CaSR mRNA (I/R: 2.62 ± 0.41, control: 1.00 ± 0.31, P < 0.01) and cardiomyocyte apoptosis [I/R: (15.32 ± 2.54)%, control: (2.90 ± 1.45)%, P < 0.01]. GdCl(3) further increased the expression of CaSR mRNA (GdCl(3): 4.46 ± 0.62, I/R: 2.62 ± 0.41, P < 0.01) and cardiomyocyte apoptosis [GdCl(3): (25.36 ± 2.60)%, I/R: (15.32 ± 2.54)%, P < 0.01], along with upregulation of Caspase-3 (GdCl(3): 1.93 ± 0.28, I/R: 1.50 ± 0.21, P < 0.01), downregulation of Bcl-2 (GdCl(3): 0.82 ± 0.18, I/R: 1.71 ± 0.30, P < 0.01) and PI3K phosphorylation inhibition (I/R: 0.87 ± 0.08, GdCl(3): 0.61 ± 0.07, P < 0.01). Combination of GdCl(3) with LY294002 further enhanced cardiomyocytes apoptosis [GdCl(3) + LY294002: (32.6 ± 3.42)%, GdCl(3): (25.36 ± 2.60)%, P < 0.01] but did not affect CaSR mRNA expression (GdCl(3) + LY294002: 4.27 ± 0.56, GdCl(3): 4.46 ± 0.62, P > 0.05). HGF decreased I/R- and GdCl(3)-induced apoptosis [GdCl(3) + HGF: (11.8 ± 1.89)%, GdCl(3): (25.36 ± 2.60)%, P < 0.05] by suppressing Caspase-3 (GdCl(3) + HGF: 1.12 ± 0.23, (GdCl(3): 1.93 ± 0.28, P < 0.05; GdCl(3) + HGF + LY294002: 1.87 ± 0.31, GdCl(3) + LY294002: 3.86 ± 0.47, P < 0.05) and promoting Bcl-2 (GdCl(3) + HGF: 2.56 ± 0.54, GdCl(3): 0.82 ± 0.18, P < 0.05; GdCl(3) + HGF + LY294002: 1.68 ± 0.28, GdCl(3) + LY294002: 0.68 ± 0.13, P < 0.05) and PI3K phosphorylation expression (GdCl(3) + HGF: 2.87 ± 0.21, GdCl(3): 0.61 ± 0.07, P < 0.05; GdCl(3) + HGF + LY294002: 2.01 ± 0.14, GdCl(3) + LY294002: 0.44 ± 0.10, P < 0.05) in accordance with downregulation of CaSR mRNA expression (GdCl(3) + HGF: 1.46 ± 0.37, GdCl(3): 4.46 ± 0.62, P < 0.01). CONCLUSION: HGF exerts protective role in I/R-induced apoptosis at least in part by inhibiting CaSR mRNA expression along with promoting Bcl-2, suppressing Caspase-3 expression and stimulating PI3K phosphorylation signaling pathway.

Improvement of heart function in postinfarct heart failure swine models after hepatocyte growth factor gene transfer: comparison of low-, medium- and high-dose groups.

Despite advances in surgical and reperfusion therapy, there is no effective therapy currently exists to prevent the progressive decline in cardiac function following myocardial infarction. Hepatocyte growth factor has potent angiogenic and anti-apoptotic activities. The aim of this study was to investigate the therapeutic effect and dose-effect relationship on postinfarction heart failure with different doses of adenovirus-mediated human hepatocyte growth factor (Ad(5)-HGF) transference in swine models. Totally twenty swine were randomly divided into four groups: (a) control group (null- Ad(5), 1 ml); (b) low-dose group (1 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (c) medium-dose group (5 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (d) high-dose group (1 x 10(10) Pfu/ml Ad(5)-HGF, 1 ml). Four weeks after left anterior descending coronary artery (LAD) ligation, different doses of Ad(5)-HGF were transferred in three therapeutic groups via right coronary artery. Four and seven weeks after LAD ligation, gate cardiac perfusion imaging was performed to evaluate cardiac perfusion and left ventricular ejection fraction (LVEF). Seven weeks after surgery, the apoptotic index of cardiocyte was observed by TUNEL, the expression of Bcl-2, Bax, alpha-SMA and Factor VIII in the border zones were evaluated by immunohistochemistry, respectively. Four weeks after myocardial infarction, no significant difference was observed among four groups. Three weeks after Ad(5)-HGF transfer, the improvement of cardiac perfusion and LVEF was obviously observed, especially after 1 x 10(10) Pfu Ad(5)-HGF transfer. TUNEL assay showed that 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF treatment had a obvious reduction in the apoptotic index compared with the null-Ad(5) group, especially after 1 x 10(10) Pfu Ad(5)-HGF treatment. The expression of Bcl-2 protein was increased and the expression of Bax protein was inhibited in the 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF groups compared with the null-Ad(5) group. The vessel density of Factor VIII(+) and alpha-SMA(+) was increased in Ad(5)-HGF groups compared with the null-Ad(5) group. There were no significant differences in angiogenesis, reducing apoptosis and ameliorating heart function between the 1 x 10(9) Pfu Ad(5)-HGF group and the null-Ad(5) group. Although no statistical difference was observed between 1 x 10(10) Pfu and 5 x 10(9) Pfu Ad(5)-HGF groups, the cardiac protective effects of 1 x 10(10) Pfu Ad(5)-HGF treatment were greater than 5 x 10(9) Pfu Ad(5)-HGF treatment. Different doses of Ad5-HGF injected via noninfarct-related artery could induce angiogenesis, reduce apoptosis and ameliorate heart function, and the cardiac protective effects of 1 x 10(10) Pfu Ad5-HGF is of most significance.

Helicobacter pylori infection is associated with decreased serum levels of high density lipoprotein, but not with the severity of coronary atherosclerosis.

OBJECTIVE: The objective of this survey was to study the association between Helicobacter pylori infection and the severity of coronary atherosclerosis. METHODS: The study population consisted of 961 consecutive patients (711 males and 250 females) who underwent coronary angiography for suspected or known coronary atherosclerosis. The patients' body mass index, blood pressure, the blood lipid, blood glucose, leukocyte count (10(9)/L), neutrophil count (10(9)/L), and Helicobacter pylori-specific IgG antibodies were performed. Coronary angiograms were scored according to vessel score and Gensini's score. RESULTS: A significant association between H. pylori infection and coronary atherosclerosis as well as its severity was not find in this cross section study (p = 0.858). And, the level distribution of vessel score (p = 0.906) and Gensini's score (p = 0.905) were similar in the seropositivity group and seronegativity group of Helicobacter pylori infection. However, the level of fasting high-density lipoprotein cholesterol (mmol/L) (p = 0.013) was significantly lower in the seropositivity group than that in the seronegativity group of Helicobacter pylori infection. CONCLUSIONS: In conclusion, in the present study, a significantly correlation between Helicobacter pylori seropositivity and angiographically evaluated severity of atherosclerosis was not find. And, the present study showed a good correlation between Helicobacter pylori infection and decreased HDL cholesterol. However, the exact mechanisms need further study.