甘天翊
中国医学科学院阜外医院 心血管内科
BACKGROUND:Galectin-3 plays an important role in modulating cardiac inflammation and fibrosis. It also takes part in the pathways underlying cardiac remodeling. Therefore, LGALS3 gene, encoding galectin-3 protein, is a promising candidate for the genetic study of dilated cardiomyopathy (DCM). To date, there has been no research evaluating the association between LGALS3 gene polymorphisms and the susceptibility and prognosis of DCM.METHODS AND RESULTS:Genotyping of 4 single nucleotide polymorphisms (SNPs) in the LGALS3 gene, which were reported to be functional in the literature, was performed in 279 unrelated clinically diagnosed DCM patients and 363 apparently healthy controls from Northern Han Chinese population using iPLEX SNP Genotyping analysis on a Sequenom MassARRAY System. The frequency of G allelic polymorphism of rs1009977 and the C allelic polymorphism of rs4652 were lower in DCM patients (OR=0.77, 95% CI [0.60-0.99], P=0.045; OR=0.79, 95% CI [0.63-0.99], P=0.042, respectively). The minor variants of rs1009977 and rs4652 were associated with low susceptibility of DCM under additive genetic models (P=0.045 and P=0.040, respectively). The AA genotype of both rs2274273 and rs4644 was associated with lower left ventricular ejection fraction (recessive model, P=0.018 for both; additive model, P=0.039 for both). The G variant of rs1009977 was related with lower serum galectin-3 level in DCM patients under three genetic models (additive model, P=0.020, dominant model, P=0.020, recessive model, P=0.037). The A variant of both rs2274273 and rs4644 was associated with lower level of galectin-3 in DCM patients under additive model (P=0.032 for both) and dominant model (P=0.012 for both). None of the 4 SNPs was associated with the cardiovascular or all-cause death rate of DCM. In Conclusion, LGALS3 gene polymorphisms might be associated with the susceptibility of DCM in a Northern Han Chinese population.
Gene 2018
OBJECTIVE:We investigated the current level of knowledge of Chinese heart failure (HF) guidelines among physicians, as a reference for the promotion and transformation of HF knowledge.METHODS AND RESULTS:Physicians from 88 hospitals in 27 provinces of China completed our survey between July and December 2014. The questions covered the main points included in the Chinese HF diagnosis and treatment guidelines (2014). A total of 2146 physicians, aged 20 to 62 years (35.6 ± 7.6 years), completed the survey. The correctness rate of their answers to the 15 multiple-choice questions in the HF questionnaire was generally low (mean 32.6%). The mean correctness rate for 10 blank-filling questions about the target doses of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and β-blockers was 42.5%. On the basis of their responses, physicians whose knowledge of the guidelines was "excellent," "good," "medium," and "bad" accounted for 1.1%, 11.4%, 14.2%, and 73.4%, respectively. Physicians who possessed a higher level of qualifications had significantly greater awareness of HF guidelines than those with relatively low qualifications (P < .001). A statistically significant association was found between hospital level and adherence to treatment guidelines (P < .001). A significant difference was also observed among physicians in different practice scopes (P < .001).CONCLUSIONS:The survey found an obvious deficiency in physicians' mastery of fundamental knowledge about HF. There is a need to improve physicians' education about HF in China.
Quality management in health care 2017
Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury. Further, we show that miR-23a directly regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. Our study reveals a novel model regulating cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study provides a new method to tackling apoptosis related cardiac diseases.
Molecules and cells 2017
C/EBPB is a crucial transcription factor, participating in a variety of biological processes including cell proliferation, differentiation and development. In the cardiovascular system, C/EBPB-CITED4 signaling is known as a signaling pathway mediating exercise-induced cardiac growth. After its exact role in exercised heart firstly reported in 2010, more and more evidence confirmed that. MicroRNA (e.g. miR-222) and many molecules (e.g. Alpha-lipoic acid) can regulate this pathway and then involve in the cardiac protection effect induced by endurance exercise training. In addition, in cardiac growth during pregnancy, C/EBPB is also a required regulator. This chapter will give an introduction of the C/EBPB-CITED4 signaling and the regulatory network based on this signaling pathway in exercised heart.
Advances in experimental medicine and biology 2017
Circular RNAs (circRNAs) have important roles in several cellular processes. No study has established the pathophysiological role for circRNAs in the heart. Here, we show that a circRNA (mitochondrial fission and apoptosis-related circRNA (MFACR)) regulates mitochondrial fission and apoptosis in the heart by directly targeting and downregulating miR-652-3p; this in turn blocks mitochondrial fission and cardiomyocyte cell death by suppressing MTP18 translation. MTP18 deficiency reduces mitochondrial fission and suppresses cardiomyocyte apoptosis and MI. miR-652-3p directly downregulates MTP18 and attenuates mitochondrial fission, cardiomyocyte apoptosis, and MI in vitro and in vivo. MFACR directly sequesters miR-652-3p in the cytoplasm and inhibits its activity. MFACR knockdown in cardiomyocytes and mice attenuates mitochondrial fission and MI. Our results reveal a crucial role for circRNA in regulating mitochondrial dynamics and apoptosis in the heart; as such, circRNAs may serve as a potential therapeutic avenue for cardiovascular diseases.
Cell death and differentiation 2017
Circular RNA (circRNA), a novel type of endogenous noncoding RNA (ncRNA), has become a research hotspot in recent years. CircRNAs are abundant and stably exist in creatures, and they are found with covalently closed loop structures in which they are quite different from linear RNAs. Nowadays, an increasing number of scientists have demonstrated that circRNAs may have played an essential role in the regulation of gene expression, especially acting as miRNA sponges, and have described the potential mechanisms of several circRNAs in diseases, hinting at their clinical therapeutic values. In this review, the authors summarized the current understandings of the biogenesis and properties of circRNAs and their functions and role as biomarkers in cardiovascular diseases.
BioMed research international 2017
BACKGROUND:Heart failure (HF) remains a significant cause of morbidity and mortality. Multiple trials over the past several years have examined the effects of both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in the treatment of left ventricular dysfunction, both acutely after myocardial infarction and in chronic heart failure. Yet, there is still confusion regarding the relative efficacy of rennin-angiotensin-aldosterone system (RAAS) inhibition. Our study was conducted to assess efficacy of ACEIs and ARBs in reducing all-cause and cardiovascular mortality in heart failure patients.METHODS:We included randomized clinical trials compared ACEIs and ARBs treatment (any dose or type) with placebo treatment, no treatment, or other anti-HF drugs treatment, reporting cardiovascular or total mortality with an observation period of at least 12 months. Data sources included Pubmed, EMBASE, the Cochrane Central Register of Controlled Trials. Dichotomous outcome data from individual trials were analyzed using the risk ratio measure and its 95%CI with random-effects/ fixed-effects models. We performed meta-regression analyses to identify sources of heterogeneity. All-cause mortality and CV mortality were thought to be the main outcomes.RESULTS:A total of 47,662 subjects were included with a mean/median follow-up ranged from 12 weeks to 4.5 years. Of all 38 studies, 32 compared ACEIs with control therapy (included 13 arms that compared ACEIs with placebo, 10 arms in which the comparator was active treatment and 9 arms that compared ACEIs with ARBs), and six studies compared ARBs with placebo. ACEIs treatment in patients with HF reduced all-cause mortality to 11% (risk ratio (RR): 0.89, 95% confidence interval (CI): 0.83-0.96, p = 0.001) and the corresponding value for cardiovascular mortality was 14% (RR: 0.86, 95% CI: 0.78-0.94, p = 0.001). However, ARBs had no beneficial effect on reducing all-cause and cardiovascular mortality. In head-to-head analysis, ACEIs was not superior to ARBs for all-cause mortality and cardiovascular deaths.CONCLUSIONS:In HF patients, ACEIs, but not ARBs reduced all-cause mortality and cardiovascular deaths. Thus, ACEIs should be considered as first-line therapy to limit excess mortality and morbidity in this population.
BMC cardiovascular disorders 2017
BACKGROUND:Contemporary data on the epidemiology of heart failure (HF) in China are scarce. The China-HF Registry was designed to investigate clinical characteristics, management, and outcomes of patients hospitalized for HF in China.METHODS AND RESULTS:Data were collected prospectively on 13,687 patients with a primary discharge diagnosis of HF who were enrolled from 132 participating hospitals from January 2012 to September 2015. Data from the China-HF Registry was compared with previously published literature. The mean age was 65 ± 15 years, 59.1% were male, and 36.0% had preserved ejection fraction. Age, body mass index, and systolic blood pressure were lower than in high-income countries. Common comorbidities included hypertension (50.9%), coronary heart disease (49.6%), and atrial fibrillation (24.4%). The overall use of diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB), and β-blockers at admission was 30.1%, 27.0%, and 25.6%, respectively, which was lower than in other registries. For patients discharged alive, ACEI/ARB, β-blocker, and mineralocorticoid receptor antagonist use in patients with reduced ejection fraction was 67.5%, 70.0%, and 74.1%, respectively; device use was much lower. The median length of hospital stay was 10 (range 7-15) days, and in-hospital mortality was 4.1 ± 0.3%. Predictors of mortality included low systolic blood pressure, acute myocardial infarction, infection, right bundle branch block, and elevated total bilirubin and blood urea nitrogen level.CONCLUSIONS:Several important findings in patient profile and treatment patterns among Chinese patients with HF were noted compared with published literature. These data underscore the need for regional characterization of HF for global clinical trials and for the identification of several quality improvement opportunities.
Journal of cardiac failure 2017
BACKGROUND:There has been no research evaluating the association between human Neuregulin (NRG) 1/ErbB2/ErbB4 gene polymorphisms and heart failure risk.METHODS AND RESULTS:Genotyping of 13 single nucleotide polymorphisms (SNPs) in the NRG-1/ErbB2/ErbB4 genes was performed in 569 unrelated heart failure patients and 682 healthy controls from a Northern Han Chinese population with the use of iPlex SNP Genotyping analysis on a Sequenom Massarray System. In the ErbB4 gene, the variants rs10932374 and rs1595064 were associated with reduced risk of heart failure under allelic, recessive and additive genetic models, and the variants rs13003941 and rs1595065 were associated with increased risk of heart failure under allelic, dominant, and additive models. The G-G-C-C-T haplotype of rs10932374-rs13003941-rs1595064-rs1595065-rs3748960 in the ErbB4 gene increased the risk of heart failure (odd ratio 1.35, 95% confidence interval [CI] 1.06-1.70; P = .014). The T variant of rs13003941 was associated with larger left ventricle (dominant model, P = .014; additive model, P = .048), and increased risk of overall death (relative risk [RR] 1.48, 95% CI 1.01-2.18; P = .045) and cardiovascular death (RR 1.56, 95% CI 1.04-2.33; P = .03) after adjusting for age and sex. NRG-1/ErbB2 gene polymorphisms were not associated with heart failure risk or prognosis.CONCLUSION:ErbB4 gene polymorphisms were associated with the risk, severity, and prognosis of heart failure in a Northern Han Chinese population.
Journal of cardiac failure 2016
BACKGROUND:Qiliqiangxin (QL) capsule is a traditional Chinese medicine which has been approved for the treatment of chronic heart failure. Evidences proved that QL capsules further reduced the NT-proBNP levels and improved left ventricular ejection fraction in CHF patients but the evidence supporting its underlying mechanism is still unclear.METHODS AND RESULTS:Myocardial infarction (MI) -Heart failure (HF) Sprague-Dawley ratsmodel and neonatal rat cardiac myocytes (NRCMs) were used. Animals were assigned into 4 groups, normal group (n=6), shame-operation group (n=6), MI rats 4 weeks after left anterior descending coronary artery ligation were randomized into vehicle group (n=8), QL group (n=8). QL significantly attenuated cardiac dysfunction and ventricle remodeling as echocardiography and hemodynamic measurements showed improvement in left ventricular ejection fraction, fractional shortening, ±dp/dt and left ventricular end diastolic and systolic diameters in QL treated group compared with the vehicle group. Improvements ininterstitial fibrosisand mitochondrial structures were also exhibited by Sirius Red staining, RT-PCR and electron microscopy. QL treatment improved apoptosis and VEGF expression in rats marginal infract area. Complementary experiments analyzed the improved apoptosis and up-regulate of VEGF in ischemia-hypoxia cultivated NRCMs is in an Akt dependent manner and can be reversed by Akt inhibitor.CONCLUSION:QL capsule can improve cardiac dysfunction and ventricular remodeling in MI-HF ratsmodel, this cardiac protective efficacy may be concerned with attenuated apoptosis and cardiac fibrosis. Up-regulated VEGF expression and Akt phosphorylation may take part in this availability.
American journal of translational research 2016
