AKT-mTOR signaling-mediated rescue of PRKAG2 R302Q mutant-induced familial hypertrophic cardiomyopathy by treatment with ß-adrenergic receptor (ß-AR) blocker metoprolol.

Background: Protein kinase AMP-activated non-catalytic subunit gamma 2 gene (PRKAG2) cardiac syndrome, caused by mutations in PRKAG2, often shows myocardial hypertrophy and abnormal glycogen deposition in cardiomyocytes. However, it remains incurable due to a lack of a management guideline for treatment. Methods: We constructed a fluorescently labeled adenovirus carrying the wild-type or R302Q mutant of the PRKAG2 gene, infected neonatal rat cardiomyocytes (NRCMs) and H9C2 cell lines, and then analyzed changes in AMP-activated protein kinase (AMPK) activity, cell hypertrophy, glycogen storage, and cell proliferation when presence or absence of metoprolol or protein kinase A (PKA) inhibition H89, and then analyzed the changes in AKT-mTOR signal transduction activity. Results: Overexpression of PRKAG2 R302Q in primary cardiomyocytes increased the activity of AMPK, induced cellular hypertrophy and glycogen storage, and promoted the phosphorylation levels of AKT-mTOR signaling pathway. Application of either ß1-adrenergic receptor (ß1-AR) blocker metoprolol or PKA inhibitor H89 to the cardiomyocytes rescued the hypertrophic cardiomyopathy (HCM)-like phenotypes induced by PRKAG2 R302Q, including suppression of both AKT-mTOR phosphorylation and AMPK activity. Conclusions: The current study not only determined the mechanism regulating HCM induced by PRKAG2 R302Q mutant, but also demonstrated a therapeutic strategy using ß1-AR blocker to treat the patients with PRKAG2 cardiac syndrome.

Integrated Bioinformatics Algorithms and Experimental Validation to Explore Robust Biomarkers and Landscape of Immune Cell Infiltration in Dilated Cardiomyopathy.

Background: The etiology of dilated cardiomyopathy (DCM) is unclear. Bioinformatics algorithms may help to explore the underlying mechanisms. Therefore, we aimed to screen diagnostic biomarkers and identify the landscape of immune infiltration in DCM. Methods: First, the CIBERSORT algorithm was used to excavate the proportion of immune-infiltration cells in DCM and normal myocardial tissues. Meanwhile, the Pearson analysis and principal component analysis (PCA) were used to identify immune heterogeneity in different tissues. The Wilcoxon test, LASSO regression, and machine learning method were conducted to identify the hub immune cells. In addition, the differentially expressed genes (DEGs) were screened by the limma package, and DEGs were analyzed for functional enrichment. In the protein-protein interaction (PPI) network, multiple algorithms were used to calculate the score of each DEG for screening the hub genes. Subsequently, external datasets were used to further validate the expression of hub genes, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy. Finally, we examined the expression of hub biomarkers in animal models. Results: A total of 108 DEGs were screened, and these genes may be related to biological processes such as cytolysis, positive regulation of cytokine secretion, etc. Two types of hub immune cells [activated natural killer (NK) cells and eosinophils] and four hub genes (ASPN, CD163, IL10, and LUM) were identified in DCM myocardial tissues. CD163 was verified to have the capability to diagnose DCM with the most excellent specificity and sensitivity. It is worth mentioning that the combined CD163 and eosinophils may have better diagnostic efficacy. Moreover, the correlation analysis showed CD163 was negatively correlated with activated NK cells. Finally, the results of the mice model also indicated that CD163 might be involved in the occurrence of DCM. Conclusion: ASPN, CD163, IL10, and LUM may have a potential predictive ability for DCM, and especially CD163 showed the most robust efficacy. Furthermore, activated NK cells and eosinophils may relate to the occurrence of DCM.

Effect of Gypenosides on Myocardial Ischemia- Reperfusion Injury and its Mechanism.

OBJECTIVES: The present study aimed to clarify the effects of Gypenosides on myocardial ischemia-reperfusion injury. Using rat H9c2 cardiomyocytes as the research object, the model of cardiomyocyte hypoxia and reoxygenation was established to observe the protective effects of Gypenosides on myocardial ischemia-reperfusion injury, revealing the key targets and possible mechanisms for Gypenosides to exert myocardial protection. MATERIAL AND METHODS: A model of cardiomyocyte hypoxia and reoxygenation was prepared. The activity of cardiomyocytes was detected by CCK-8 method. The cardiomyocyte injury was evaluated by LDH assay. The cardiomyocyte apoptosis rate was detected by flow cytometry. The mitochondrial membrane potential of cardiomyocytes was detected by JC-1 staining. Western blot was used to detect the expression of MPTP downstream apoptotic pathways and MPTP opening-related regulatory factors. RESULTS: The cell survival rate of each Gypenosides pretreatment group was significantly higher than that of the hypoxia-reoxygenation group, indicating that Gypenosides could inhibit cell apoptosis and the decrease of mitochondrial membrane potential of hypoxia-reoxygenation cells. The expressions Cytochrome C, APAFl, Caspase-9, and Caspase-3 proteins were significantly lower than those of the hypoxia-reoxygenation group, the expression of Bax was significantly lower than those of the hypoxia-reoxygenation group, while the expression of Bcl2 was significantly higher than those of the hypoxia-reoxygenation group. CONCLUSION: Gypenosides can effectively reduce myocardial ischemia-reperfusion injury in rats. By regulating Bax and Bcl2, Gypenosides can inhibit MPTP opening and the activation of downstream apoptotic pathways, thereby reducing myocardial ischemia-reperfusion injury.

Specific protein 1 inhibitor mithramycin A protects cardiomyocytes from myocardial infarction via interacting with PARP.

Specific protein 1 (SP1) might act as a critical transcription regulator in myocardial infarction (MI), but little evidence about its function in regulating cardiac apoptosis, a major cause of MI development, has been revealed. This study tried to investigate the role of SP1 in MI and its interaction with poly-ADP-ribose polymerase (PARP)-1 by using SP1 inhibitor, mithramycin A (mithA). Primary mouse cardiomyocytes and commercial mouse cardiomyocytes were subjected to mithA treatment under hypoxia conditions, while cell viability, Nix promoter activity, and its expression were detected correspondingly. PARP overexpression and knockdown were conducted, respectively, in mithA-treated and SP1-overexpressing cells. Co-immunoprecipitation was used to verify the interaction between PARP and SP1. For in vivo experiments, mithA administration was performed after the injections of adenovirus for PARP overexpression, and then, MI introduction was carried out. Infarct size and lactate dehydrogenase level were measured to assess MI injury. SP1 inhibitor mithA attenuated hypoxia-induced decrease of cell viability and Nix transcriptional activation, which could be inhibited by PARP overexpression. Knockdown of PARP prevented SP1-induced transcription of Nix and cell viability change, and PARP showed direct interaction with SP1. Furthermore, mithA administration reduced MI injuries, while PARP overexpression could suppress the improvement. The cardioprotective role of SP1 inhibitor mithA was demonstrated here expanding the role of SP1 in MI development involving hypoxia-induced cardiac apoptosis. Moreover, PARP acted as a transcriptional coactivator in Nix transcription involving its interaction with SP1.

N6-methyladenosine methyltransferase plays a role in hypoxic preconditioning partially through the interaction with lncRNA H19.

N6-methyladenosine (m6A), a methylation in the N6 position of adenosine especially in the mRNA, exerts diverse physiological and pathological functions. However, the precise role of m6A methylation in hypoxic preconditioning (HPC) is still unknown. Here, we observed that HPC treatment protected H9c2 cells against H2O2-induced injury, upregulated the m6A level in the total RNA and the expression of methyltransferase like 3 (METTL3), methyltransferase like 14 (METTL14), and long noncoding RNA (lncRNA) H19. Either knockdown of METTL3 or METTL14 notably reversed the HPC-induced enhancement of cell viability, anti-apoptosis ability, and H19 expression. Methylated RNA immunoprecipitation (IP) indicated that knockdown of METTL3 or METTL14 decreased m6A level in the lncRNA H19. Gain-of-function assay demonstrated that H19 overexpression could partially rescue the decreased protection mediated by METTL3 or METTL14 knockdown in HPC-treated H9c2 cells. RNA binding protein immunoprecipitation (RIP) assay showed that METTL3 and METTL14 could directly bind with H19. Our study identified a novel pattern of posttranscriptional regulation in HPC treatment. Since METTL3, METTL14, and lncRNA H19 were involved in HPC protection, they could be considered as potential biomarkers and therapeutic targets in HPC-derived cardiac rehabilitation and therapeutic approaches.

Effects of Polymorphisms in Pre-miRNA on Inflammatory Markers in Atrial Fibrillation in Han Chinese.

BACKGROUND: MicroRNA molecules have been identified to play key roles in a broad range of physiological and pathological processes. Polymorphisms in the corresponding sequence space are likely to make a significant con-tribution to phenotypic variation. The aim of this study was to evaluate the pre-miR-146a C/G (rs2910164) and pre-miR-499 T/C (rs3746444) polymorphisms and their putative association with inflammatory markers in AF in Han Chinese. METHODS: A total of 123 participants were enrolled, 65 AF patients were confirmed with electrocardiogram (ECG) or dynamic electrocardiography, 58 normal individuals were assigned to the control group. RESULTS: Genotypes of the pre-miR-146a C/G (rs2910164) and pre-miR-499 T/C (rs3746444) polymorphisms were distinguished using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The distribution of the pre-miR-146a C/G (rs2910164) genotypes CC, CG, and GG was 33.85%, 52.31%, and 13.84% in the AF group and 37.93%, 51.72%, and 10.35% in the controls, respectively. There was no significant difference in either genotype frequency distributions (p = 0.7973) or allele frequency distributions (p = 0.5411) between these two groups. The distribution of the pre-miR-499 T/C (rs3746444) genotypes TT, TC, and CC was 72.41%, 22.41%, and 5.18% in the controls and 49.23%, 38.46%, and 12.31% in AF subjects, respec-tively (p = 0.0296). The frequency of the C allele in the AF group was significantly higher than that in the control group (31.54% vs. 16.38%, p = 0.0057). Compared with the TT genotype, the C allele carriers (TC+CC genotypes) had a 2.7070-fold increased risk of AF. After being adjusted for age, gender, leucocytes, left atrial dimension, left ventricular ejection fraction, serum levels of lipids, and inflammatory markers, the association persisted (adjusted OR = 2.3387, 95% CI =1.1094 - 4.9300, p = 0.0280). Individuals with TC+CC genotype in pre-miR-499 T/C (rs3746444) had greater serum levels of IL-6 and hs-CRP than did patients with the TT genotype. CONCLUSIONS: Our data support that the pre-miR-499 T/C (rs3746444) polymorphism is associated with AF, and the C allele has increased risk for AF in Han Chinese.

Outcomes after percutaneous coronary intervention and comparison among scoring systems in predicting procedural success in elderly patients (≥ 75 years) with chronic total occlusion.

BACKGROUND: Evidence-based data on percutaneous coronary intervention in elderly patients with chronic total occlusion (CTO) and comparison among different scoring systems have not been well established. PATIENTS AND METHODS: A total of 246 consecutive patients were stratified into two groups according to the age: elderly group (age≥ 75 years, n = 68) and nonelderly group (age < 75 years, n = 178). Clinical and angiographic characteristics including the Synergy Between PCI With TAXUS and Cardiac Surgery score, in-hospital major adverse cardiac events, procedural success rates, and predictive capacity of four scoring systems [J-CTO, Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS CTO), clinical and lesion-related (CL), and ostial location, Rentrop grade < 2, age ≥ 75 years (ORA) scores] were examined. RESULTS: Triple-vessel disease and the Synergy Between PCI With TAXUS and Cardiac Surgery score in the elderly group were significantly higher than those in the nonelderly group (73.53 vs. 53.93%, P = 0.005; 31.39 ± 7.68 vs. 27.85 ± 7.16, P = 0.001, respectively). The in-hospital major adverse cardiac event rates, vascular access complication rates, and major bleeding rates were similar between the elderly and the nonelderly group (2.94 vs. 2.25%, P = 0.669; 1.47 vs. 0.56%, P = 0.477; 2.94 vs. 1.12%, P = 0.306, respectively). By contrast, the procedural success rate was statistically lower in the elderly group than that in the nonelderly group (73.53 vs. 84.83%, P = 0.040). All the four scoring systems showed a moderate predictive capacity [area under the curve (AUC) for J-CTO score: 0.806, P < 0.0001; AUC for PROGRESS CTO score: 0.727, P < 0.0001; AUC for CL score: 0.800, P < 0.0001; AUC for ORA score: 0.672, P < 0.0001, respectively]. Compared with the ORA score, the J-CTO score, and the CL score showed a significant advantage in predicting procedural success among overall patients (ΔAUC = 0.134, P = 0.0122; ΔAUC = 0.128, P = 0.0233, respectively). CONCLUSION: Despite the lower procedural success rate, percutaneous coronary intervention in elderly patients with CTO is feasible and safe. J-CTO, PROGRESS, ORA, and CL scoring systems have moderate discriminatory capacity.

Triglyceride to high-density lipoprotein cholesterol ratio as a risk factor of repeat revascularization among patients with acute coronary syndrome after first-time percutaneous coronary intervention.

BACKGROUND: It is clinically important to identify high-risk patients with acute coronary syndrome (ACS) who may require repeat revascularization. This retrospective study identified risk factors for repeat revascularization among ACS patients after first-time successful percutaneous coronary interventions (PCIs). The predictive value of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio for repeat revascularization was also evaluated. METHODS: We enrolled consecutive ACS patients who had coronary angiography performed during the period from 6 to 12 months after a first-time successful PCI. The primary outcome of the study was to identify the risk factors of repeat revascularization. The subjects were stratified based on repeat PCI events. After comparing various clinical characteristics, univariate and multivariate Cox proportional hazard model analyses were adopted to evaluate the effects of risk factors on repeat revascularization. RESULTS: The patients (n=271) were divided into the event (+) group (n=101) and the event (-) group (n=170). In the event (+) group, target lesion revascularization (TLR) accounted for 20.79% and target vessel revascularization (TVR) accounted for 50.49% of the patients. In contrast, 52.47% of the patients required de novo vessel revascularization (DVR). After adjustment for confounding factors, the TG/HDL-C ratio [hazard ratio (HR) =1.206, 95% confidence interval (CI): 1.016-1.431, P=0.032 for each higher TG/HDL-C ratio unit] and the Gensini score (HR =1.012, 95% CI: 1.005-1.018, P<0.001 for each higher Gensini score unit) were independent risk factors for a repeat PCI. Subgroup analyses showed that higher TG/HDL-C ratios were associated with a significantly higher risk of repeat PCIs in the male, hypertensive, and diabetes mellitus subgroups. CONCLUSIONS: The TG/HDL-C ratio and Gensini score could serve as risk factors for repeat revascularization in ACS patients after a first-time successful PCI.

Apixaban attenuates ischemia-induced myocardial fibrosis by inhibition of Gq/PKC signaling.

It was previously found that patients with symptom of myocardial dysfunction had increased levels of thrombin. Apixaban is one of the novel oral anticoagulant drugs widely used in clinic. As the inhibitor of FXa (prothrombin), it inhibits prothrombin conversion into thrombin leading to thrombin deficiency in vivo. However, the effects of apixaban on myocardial fibrosis were still unclear, and the concomitant molecular mechanisms remain to be investigated. Here, we showed that myocardial fibrosis-bearing mice induced by continuous myocardial ischemia (MI) had higher levels of thrombin. Orally administration of apixaban significantly abrogated fibrosis condition and thrombin levels. In vitro, thrombin induced collagen deposition in primary cardiac fibroblasts in a dose-dependent manner. Mechanistic experiments showed that thrombin induced collagen deposition by activation of the Par-1-coupled Gq/PKC signaling. Genetic ablation of Gq or pharmacological inhibition of PKC effectively blunted thrombin-induced collagen deposition in cardiac fibroblasts. Moreover, administration of PKC inhibitor or Gq antagonist obviously blocked MI-induced myocardial fibrosis in mice. To conclude, apixaban attenuates MI-induced myocardial fibrosis by inhibition of thrombin-dependent Par-1/Gq/PKC signaling axis.

miR-7a/b attenuates post-myocardial infarction remodeling and protects H9c2 cardiomyoblast against hypoxia-induced apoptosis involving Sp1 and PARP-1.

miRs (microRNAs, miRNAs) intricately regulate physiological and pathological processes. Although miR-7a/b protects against cardiomyocyte injury in ischemia/reperfusion injury, the function of miR-7a/b in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Here, we sought to investigate the function of miR-7a/b in post-MI remodeling in a mouse model and to determine the underlying mechanisms involved. miR-7a/b overexpression improved cardiac function, attenuated cardiac remodeling and reduced fibrosis and apoptosis, whereas miR-7a/b silencing caused the opposite effects. Furthermore, miR-7a/b overexpression suppressed specific protein 1 (Sp1) and poly (ADP-ribose) polymerase (PARP-1) expression both in vivo and in vitro, and a luciferase reporter activity assay showed that miR-7a/b could directly bind to Sp1. Mithramycin, an inhibitor of the DNA binding activity of Sp1, effectively repressed PARP-1 and caspase-3, whereas knocking down miR-7a/b partially counteracted these beneficial effects. Additionally, an immunoprecipitation assay indicated that hypoxia triggered activation of the binding activity of Sp1 to the promoters of PARP-1 and caspase-3, which is abrogated by miR-7a/b. In summary, these findings identified miR-7a/b as protectors of cardiac remodeling and hypoxia-induced injury in H9c2 cardiomyoblasts involving Sp1 and PARP-1.

Curcumin protects cardiac myocyte against hypoxia-induced apoptosis through upregulating miR-7a/b expression.

OBJECTIVE: Curcumin has properties of anti-inflammation, anti-oxidation, anti-infection and anti-tumor, benefiting for the treatment of many diseases. The present study was aimed to investigate the role of curcumin in myocardial infarction (MI) and its potential mechanism involving transcription factor specific protein 1 (SP1). METHODS: After receiving curcumin, C57BL/6 mice subjected to left anterior descending (LAD) coronary artery occlusion to induce MI model. Infarct size was measured by triphenyl tetrazolium chloride staining. In vitro experiments, mouse cardiac myocytes (MCM) subjected to hypoxia after the incubation of curcumin, miR-7a/b and SP1 expression levels were detected by real-time PCR and western blot. Caspase-3 activity and TUNEL assay were performed to assess the cell apoptosis. RESULTS: In animal experiments, curcumin significantly reduced the infarct size compared with the control. It also up-regulated miR-7a/b expression and down-regulated SP1 expression. In hypoxia-induced MCM, curcumin led to the decrease of cell apoptosis. Transfected MCM with miR-7a/b inhibitor, curcumin induced the decrease of cell apoptosis and SP1 expression was reversed. Transfected with pcDNA-SP1, the decrease of cardiac myocytes apoptosis after the treatment of curcumin was also reversed. CONCLUSION: Curcumin pre-treatment protected against hypoxia-induced cardiac myocytes apoptosis through the up-regulation of miR-7a/b and the down-regulation of SP1 expression.

The Circular RNA Cdr1as Promotes Myocardial Infarction by Mediating the Regulation of miR-7a on Its Target Genes Expression.

OBJECTIVES: Recent studies have demonstrated the role of Cdr1as (or CiRS-7), one of the well-identified circular RNAs (circRNAs), as a miR-7a/b sponge or inhibitor in brain tissues or islet cells. This study aimed to investigate the presence of Cdr1as/miR-7a pathway in cardiomyocytes, and explore the mechanism underlying the function of miR-7a in protecting against myocardial infarction (MI)-induced apoptosis. METHODS: Mouse MI injury model was established and evaluated by infarct size determination. Real-time PCR was performed to quantify the expression of Cdr1as and miR-7a in cardiomyocytes. Cell apoptosis was determined by caspase-3 activity analysis and flow cytometry assays with Annexin V/PI staining. Transfection of Cdr1as overexpressing plasmid and miR-7a mimic were conducted for gain-of-function studies. Luciferase reporter assay and western blot analysis were performed to verity potential miR-7a targets. RESULTS: Cdr1as and miR-7a were both upregulated in MI mice with increased cardiac infarct size, or cardiomyocytes under hypoxia treatment. Cdr1as overexpression in MCM cells promoted cell apoptosis, but was then reversed by miR-7a overexpression. The SP1 was identified as a new miR-7a target, in line with previously identified PARP, while miR-7a-induced decrease of cell apoptosis under hypoxia treatment was proven to be inhibited by PARP-SP1 overexpression. Moreover, Cdr1as overexpression in vivo increased cardiac infarct size with upregulated expression of PARP and SP1, while miR-7a overexpression reversed these changes. CONCLUSIONS: Cdr1as also functioned as a powerful miR-7a sponge in myocardial cells, and showed regulation on the protective role of miR-7a in MI injury, involving the function of miR-7a targets, PARP and SP1.

Clinical Outcomes of Revascularization Strategies for Patients With MVD/LMCA Disease: A Systematic Review and Network Meta-Analysis.

Hybrid coronary revascularization (HCR), a new minimally invasive procedure for patients requiring revascularization for multivessel coronary lesions, combines coronary artery bypass grafting (CABG) for left anterior descending (LAD) lesions and percutaneous coronary intervention (PCI) for non-LAD coronary lesions. However, available data related to outcomes comparing the 3 revascularization therapies is limited to small studies.We conducted a search in MEDLINE, EMBASE, and the Cochrane Library of Controlled Trials up to December 31, 2014, without language restriction. A total of 16 randomized trials (n=4858 patients) comparing HCR versus PCI or off-pump CABG (OPCAB) were included in this meta-analysis. The primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), all-cause death, myocardial infarction (MI), cerebrovascular events (CVE), and target vessel revascularization (TVR). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effect and fixed-effect models. Ranking probabilities were used to calculate a summary numerical value: the surface under the cumulative ranking (SUCRA) curve.No significant differences were seen between the HCR and PCI in short term (in hospital and 30 days) with regard to MACCE (odds ratio [OR] = 0.51, 95% confidence interval [CI] 0.00-2.35), all-cause death (OR = 2.09, 95% CI 0.34-7.66), MI (OR = 1.02, 95% CI 0.19-2.95), CVE (OR = 4.45, 95% CI 0.39-19.16), and TVR (OR = 6.99, 95% CI 0.17-39.39). However, OPCAB had lower MACCE than HCR (OR = 0.19, 95% CI 0.00-0.95). In midterm (1 year and 3 year), in comparison with HCR, PCI had higher all-cause death (OR = 5.66, 95% CI 0.00-13.88) and CVE (OR = 4.40, 95% CI 0.01-5.68), and lower MI (OR = 0.51, 95% CI 0.00-2.86), TVR (OR = 0.53, 95% CI 0.05-2.26), and thus the MACCE (OR = 0.51, 95% CI 0.00-2.35). Off-pump CABG presented a better outcome than HCR with significant lower MACCE (OR = 0.17, 95% CI 0.01-0.68). Surface under the cumulative ranking probabilities showed that HCR may be the superior strategy for MVD and LMCA disease when regarded to MACCE (SUCRA = 0.84), MI (SUCRA = 0.76) in short term, and regarded to MACCE (SUCRA = 0.99), MI (SUCRA = 0.94), and CVE (SUCRA = 0.92) in midterm.Hybrid coronary revascularization seemed to be a feasible and acceptable option for treatment of LMCA disease and MVD. More powerful evidences are required to precisely evaluate risks and benefits of the 3 therapies for patients who have different clinical characteristics.

In-hospital clinical outcomes of elderly patients (≥60 years) undergoing primary percutaneous coronary intervention.

Elderly patients are at high risk of mortality when they present with ST-elevation myocardial infarction (STEMI). However, the clinical outcomes of this sub-group undergoing primary percutaneous coronary intervention (PPCI) have not been well established, despite recent advances in both devices and techniques. In the present retrospective cohort study from a Chinese single center, we assessed the clinical outcomes and predictors of mortality in elderly patients (≥60 years) underwent with PPCI. The primary endpoints were immediate angiographic success and in-hospital procedural success. The secondary endpoints were all-cause death in hospital. Between January 2011 and December 2013, a total of 184 consecutive patients with acute STEMI underwent PPCI were enrolled. 116 (63.04%) patients were in the elderly group. Despite the difference in lesion complexity between groups, the immediate angiographic success rate was similar (93.97% in the elderly group, and 94.12% in the non-elderly group, P=0.966). The procedural success rate were not significantly different between the two groups (90.52% in the elderly group, and 94.12% in the non-elderly group, P=0.389). However, in-hospital mortality was statistically higher in elderly group than in the non-elderly group (8.62% Vs 1.47%, P=0.048). The major causes of death were cardiac shock and malignant arrhythmias (ventricular tachycardia and fibrillation). Our results indicate that PPCI in the elderly is feasible and has a high likelihood of immediate angiographic and procedural success.

Interleukin-6 promotor polymorphisms and coronary vasospastic angina in Han Chinese.

There is an accumulating body of evidence indicating association between inflammation and the pathogenesis of coronary vasospastic angina (CVA). Interleukin-6 (IL-6) is a pleiotropic cytokine, functions as a mediator of inflammatory response and has both pro-inflammatory and anti-inflammatory properties. The aim of the present study is to investigate the association of -634C/G polymorphism of IL-6 gene with CVA in Han Chinese. A total of 27 CVA patients and 232 healthy controls were eligible for this study. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes frequencies. The distribution of the IL-6 -634C/G genotypes (CC, CG, and GG) was 59.48%, 37.07%, and 3.45% in the controls, and 37.04%, 48.15%, and 14.81% in CVA group, respectively (P = 0.0080). The frequency of the G allele in the CVA group was significantly higher than that in the control group (38.89% vs 21.98%, P = 0.0057). Compared with the wild type CC, the G allele carriers (CG + GG genotypes) had increased risk of CVA in both unadjusted and adjusted analyses. These findings suggest that IL-6 -634C/G polymorphism is associated with CVA and the G allele is an independent risk for CVA in Han Chinese.

A functional single-nucleotide polymorphism in interleukin-6 promoter is associated with p wave dispersion in hypertensive subjects with atrial fibrillation.

Inflammation has been shown to be implicated in the pathophysiology of atrial fibrillation (AF). Interleukin-6 (IL-6) is a pleiotropic cytokine, functions as a mediator of inflammatory response and has both pro-inflammatory and anti-inflammatory properties. Little is known about genetic factors of inflammation in the accompanying atrial electrical remodeling expressed by P wave dispersion (Pdisp). The aim of the present study is to evaluate the association of -634C/G polymorphism of IL-6 gene with Pdisp in Han Chinese hypertensive patients with AF. A total of 100 patients with essential hypertension (EH) were eligible for this study. Patients with paroxysmal AF (n=50) were allocated to the AF group, and 50 subjects without AF to the control group. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes frequencies. The distribution of the IL-6 -634C/G genotypes (CC, CG, and GG) was 68.00%, 28.00%, and 4.00% in the controls, and 44.00%, 40.00%, and 16.00% in AF subjects, respectively (P=0.0269). The frequency of the G allele in the AF group was significantly higher than that in the control group (36.00% vs 18.00%, P=0.0041). Compared to the wild type CC, the G allele carriers (CG + GG genotypes) had a 2.7045-fold increased risk of AF (odds ratio =2.7045, 95% confidence interval =1.1966-6.1126, P=0.0156). AF patients with the CG + GG genotype had longer Pdisp (P=0.0032) than did patients with the CC genotype. The longer Pdisp in the subjects with the CG + GG genotype was also found in the control group (P=0.0016). These findings support that IL-6 -634C/G polymorphism is associated with Pdisp and AF, suggesting an active implication of inflammation in the atrial electrophysiological remodeling predisposing to AF.

Interleukin-6 -634C>G polymorphism in hypertensive patients with and without left ventricular hypertrophy.

There is an accumulating body of evidence indicating that inflammation plays a pivotal role in the pathogenesis of cardiovascular disease. Interleukin-6 (IL-6) is a pleiotropic cytokine secreted by many cells of the immune system, cardiovascular components and adipose tissue, and functions as a mediator of inflammatory response with both pro- and anti-inflammatory properties. Circulating levels of IL-6 differ greatly between individuals due to both genetic and environmental factors. The IL-6 -634C>G polymorphism is common in eastern Asian populations. The aim of the present study was to investigate the association of this polymorphism with essential hypertension (EH) and left ventricular hypertrophy (LVH) in 440 subjects (246 EH patients and 194 controls) from a Han Chinese population. In this study, IL-6 -634C>G genotypes were identified by polymerase chain reaction and restriction digestion in all study participants, and left ventricular mass was assessed by 2-mode echocardiography in 178 untreated EH patients. There was no significant difference in either genotype distribution (p=0.9528) or allele frequency (p=0.7775) between the EH and control groups. In addition, the -634C>G polymorphism had no effect on blood pressure in either the controls or the untreated EH patients. No significant differences in genotype distribution (p=0.7998) or allele frequency distribution (p=0.5468) were found between EH patients with and without LVH. Moreover, the echocardiographic parameters were not statistically different between the CC and CG+GG genotypes. These findings suggest that there is no association of the IL-6 -634C>G polymorphism and EH with LVH in EH patients.

Apolipoprotein E polymorphism in normal Han Chinese population: frequency and effect on lipid parameters.

Apolipoprotein E (ApoE) genotypes were studied in order to determine the prevalence and effect on lipid parameters in normal Han Chinese population. Fragments of ApoE gene forth exon containing codon 112 and 158 polymorphic locus were amplified by PCR, and then digested with Cfo I endonuclease. Genotypes and alleles frequencies of 168 healthy Han Chinese were calculated. The frequency of genotypes epsilon3/3, epsilon3/4, and epsilon2/3 was found to be 75.00, 10.70, and 11.90%, respectively, and 0.60, 1.20, and 0.60% for epsilon2/2, epsilon2/4, and epsilon4/4. The effects of ApoE genotypes and alleles on lipid parameters were analyzed. The effects of ApoE alleles on TC, LDL-C, ApoB was: along a decreasing gradient epsilon4 > epsilon3 > epsilon2. The effect of epsilon4 allele was to increase serum levels of TC, LDL-C and ApoB, and epsilon2 allele had an effect opposite to that of epsilon4 allele. Results obtained in this study indicate that ApoE polymorphism is an independent genetic factor on individual serum levels of lipids and apolipoproteins.

Association of angiotensin-converting enzyme gene 2350G>A polymorphism with myocardial infarction in a Chinese population.

Angiotensin-converting enzyme (ACE) gene 2350G>A polymorphism has the most significant effect on plasma ACE concentrations. But the association between this polymorphism and myocardial infarction (MI) is presently unknown. We carried out a case-control study in the Chinese Han population. ACE2350G>A genotypes of 231 patients with MI and 288 healthy controls were detected by PCR-RFLP. Differences in frequencies of ACE genotypes and alleles and their associations with clinical features were assessed. The distribution of the ACE2350G>A genotypes (GG, GA, and AA) was 20.78%, 51.08%, and 28.14% in the MI group and 31.60%, 46.53%, and 21.87% in controls, respectively (P = .0167).The frequency of the A allele in the MI group was significantly higher than that in controls (53.68% vs 45.14%, P = .0062). The A allele carriers (GA + AA genotypes) had approximately 2-fold increased risk of MI when compared with the GG genotype (odds ratio = 1.76; 95% confidence interval = 1.24-3.52). There were no significant differences among the 3 genotypes in plasma levels of lipids, apolipoproteins, high-sensitivity C-reactive protein, and soluble CD40 ligand in either the MI group or the control group (P > .05). No statistical difference was observed between ACE2350G>A polymorphism and severity of the coronary lesions (P > .05). These results suggest that ACE2350G>A polymorphism is associated with acute MI, and A allele carrier is an independent risk factor for acute MI in the Chinese Han population.