Jiechun Huang

Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway

Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α.

Preoperative Insertion of an Intra-Aortic Balloon Pump Improved the Prognosis of High-Risk Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

This study investigated the efficacy and safety of preoperative insertion of an intra-aortic balloon pump (IABP) in high-risk coronary atherosclerotic disease patients undergoing off-pump coronary artery bypass grafting (OPCAB). A total of 232 patients were recruited to the study, of whom 107 underwent percutaneous insertion of an IABP prior to OPCAB. The remaining 125 patients underwent OPCAB alone. Pre-, peri- and postoperative parameters were compared between the two groups. Preoperative insertion of an IABP was associated with a shorter stay in intensive care, decreased incidence of postoperative dialysis and acute heart failure, and a reduction in postoperative mortality compared with OPCAB alone. There were no between-group differences in terms of haematocrit level, number of distal anastomoses, volume of postoperative drainage or incidence of reoperation for bleeding and postoperative stroke/cerebrovascular accident. In conclusion, preoperative insertion of an IABP improved the prognosis of high-risk CAD patients undergoing OPCAB.

The Gene Polymorphism of LOX1 Predicts the Incidence of LVH in Patients with Essential Hypertension

Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been shown to play an important role in cardiac remodeling under different pathologic conditions. The role of genetic polymorphisms in the LOX1 gene, however, remains unclear in the development of left ventricular hypertrophy (LVH) for patients with hypertension. Methods: A total of 536 patients diagnosed with essential hypertension (EH) were recruited in this study. Patients were assigned to the LVH+ (n=143) and LVH- (n=393) groups, respectively. The serum LOX1 level was measured and three single nucleotide polymorphisms (SNPs), i.e. intron 4 (G→A), intron 5(T→G), and 3′ UTR (T→C) of the LOX1 gene were genotyped. Results: The genotype frequencies of intron 4 G>A and 3′UTR T>C were not significantly different between the LVH+ and LVH- groups (both P>0.05), however, frequencies of 501G>C were significantly different between those two groups (P=0.007). The 501CC genotype carriers had a markedly higher serum LOX1 level and an increased risk to develop LVH (adjusted OR=2.444, adjusted P=0.002). There was a positive correlation between serum LOX1 level and left ventricular mass index (r=0.907, P<0.001); a cutoff value of 1.0 ng/mL for sLOX-1 was applied to significantly differentiate the LVH+ patients from the LVH- patients with 84% sensitivity and 86% specificity. Conclusion: Our data suggest that both the 501>C SNP in the LOX1 gene and the serum LOX1 level may be used to predict the development of LVH among EH patients.

A Long-Term and Slow-Releasing Hydrogen Sulfide Donor Protects against Myocardial Ischemia/Reperfusion Injury

Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter exerting various physiological effects, especially in the cardiovascular system. Herein we investigated the cardioprotective effects of a novel long-term and slow-releasing H2S donor, DATS-MSN, using in vivo myocardial ischemia/reperfusion (I/R) models and in vitro hypoxia/reoxygenation cardiomyocyte models. Unlike the instant-releasing pattern of sodium hydrosulphide (NaHS), the release of H2S from DATS-MSN was quite slow and continuous both in the cell culture medium and in rat plasma (elevated H2S concentrations during 24 h and 72 h reperfusion). Correspondingly, DATS-MSN demonstrated superior cardioprotective effects over NaHS in I/R models, which were associated with greater survival rates, reduced CK-MB and troponin I levels, decreased cardiomyocyte apoptosis index, increased antioxidant enzyme activities, inhibited myocardial inflammation, greater reduction in the infarct area and preserved cardiac ejection fraction. Some of these effects of DATS-MSN were also found to be superior to classic slow-releasing H2S donor, GYY4137. In in vitro experiments, cardiomyocytes injury was also found to be relived with the use of DATS-MSN compared to NaHS after the hypoxia/reoxygenation processes. The present work provides a novel long-term and slow-releasing H2S donor and an insight into how the release patterns of H2S donors affect its physiological functionality.

HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells

BackgroundEmbryonic stem cells (ESCs) are pluripotent stem cells and can differentiate into cardiomyocytes when cultured in appropriate conditions. The function of hypoxia-inducible factors (HIFs) has been identified in directing the formation of cardiac lineages. The purpose of this study was to investigate the ability of HIF2α to induce differentiation of ESCs into cardiomyocytes and to explore the potential underlying molecular mechanisms.MethodsCardiac differentiation from mouse ESCs was analyzed using the “hanging drop” method, and success was determined by assaying the numbers of beating embryoid bodies and the expression level of cardiac markers. The expression of HIF2α was then manipulated during cardiac differentiation with piggyBac transposon and the lentivirus system. The underlying mechanism was finally examined via administering selective inhibitors of the Wnt/β-catenin signaling pathway.ResultsOverexpressing HIF2α can significantly drive mouse ESCs to form cardiomyocytes. Contrarily, knockdown of HIF2α inhibits the emergence of cardiac cells. In addition, the cardiomyogenesis-promoting effect of HIF2α occurred by increasing the protein level of β-catenin, an effector that contributes to cardiac differentiation at an early stage of ESC differentiation.ConclusionHIF2α has a cardiomyogenesis-promoting effect in ESCs via enhancing the activation of the Wnt/β-catenin signaling pathway. Our results may be beneficial for generating and applying cardiomyocytes from ESCs safely and effectively in the future.

Primary Esophageal CD30-Positive ALK-Positive Anaplastic Large Cell Lymphoma: A Case Report and Literature Review

PurposeTo introduce a case of primary esophageal CD30-positive ALK-positive anaplastic large cell lymphoma (ALCL) and discuss its diagnosis and treatment.MethodsEsophagectomy was done for a 37-year-old male with a submucosal lesion after a frozen section failed to give a definite diagnosis. Samples were sent for hematoxylin–eosin staining and immunohistochemical analysis. Six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy were given and the patient was followed up.ResultsThe operation was uneventful. Postoperative pathologic and immunohistochemical examination yielded a diagnosis of primary CD30-positive and ALK-positive ALCL of the esophagus. The patient was in complete remission at the 14-month follow-up.ConclusionsALCL of the esophagus should be considered in the differential diagnosis of esophageal submucosal lesions. Biopsy through either esophagoscopy or surgical exploration, chemotherapy, and radiotherapy can be chosen for long-term survival.

Rs12218 In SAA1 gene was associated with serum lipid levels

BackgroundSerum amyloid A (SAA) is a kind of apolipoprotein. Several studies indicated that SAA genetic polymorphism rs12218 was associated with carotid atherosclerosis, peripheral arterial disease, and serum uric acid levels. However, the relation between rs12218 and lipid levels remains unclear. This study assessed the correlation between SAA1 gene rs12218 polymorphism and lipid levels in a Chinese population.MethodsA total of 823 participants were selected from the subjects for health check in Shanghai Huashan hospital from Jan. 2013 to Mach. 2013. Correlations between rs12218 polymorphism and lipid levels were investigated through the identification of rs12218 genotypes using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsWe found that the SNP rs12218 was associated with triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels by analyses of a dominant model (P<0.001, P=0.002, P=0.003, respectively), a recessive model (P <0.001, P=0.001, P=0.005, respectively) and an additive model (P < 0.001, P=0.001, P=0.002, respectively), and the difference remained significant after the adjustment of sex, age, alcohol intake, and smoking (All P < 0.01).ConclusionOur results indicated that the rs12218 in the SAA1 gene was associated with lipid levels in a Chinese population.

Predictors of moderate ischemic mitral regurgitation improvement after off-pump coronary artery bypass

OBJECTIVE The aim of this study was to explore the predictors of improvement of moderate ischemic mitral regurgitation after off-pump coronary artery bypass grafting. METHODS A prospective study was performed among 109 patients (aged 66.6 ± 8.6 years, 34.6% were female) with prior myocardial infarction and moderate ischemic mitral regurgitation undergoing off-pump coronary artery bypass grafting. Preoperative and follow-up clinical characteristics and echocardiography data were analyzed, focusing on left ventricular global/regional remodeling and function. Patients were grouped by postoperative ischemic mitral regurgitation at 1 year postoperatively: the improved group with no or mild ischemic mitral regurgitation and the failure group with moderate or severe ischemic mitral regurgitation. Data were compared between the 2 groups to explore the predictors of ischemic mitral regurgitation improvement after off-pump coronary artery bypass grafting. RESULTS Five patients died within 1 year and were excluded. At the 1-year follow-up, there were 55 patients in the improved group and 49 patients in the failure group. Before surgery, the improved group had smaller left ventricular end-systolic volume, greater left ventricular ejection fraction, greater posterior-inferior volume ratio, and earlier operation timing after infarction than the failure group. Posterior-inferior volume ratio (P < .001), ejection fraction (P = .003), and duration between infarction and operation (P < .001) were independent predictors of preoperative moderate ischemic mitral regurgitation improvement. CONCLUSIONS In selected patients, preoperative moderate ischemic mitral regurgitation was relieved by off-pump coronary artery bypass grafting. Greater ejection fraction, greater posterior-inferior volume ratio, and early operation timing after infarction may predict the improvement of moderate ischemic mitral regurgitation after off-pump coronary artery bypass grafting, suggesting that posterior-inferior regional remodeling, reserved ventricular function, and early revascularization are important to the outcome.

Coronary artery fistula associated with mitral valve endocarditis.

Abstract  Coronary artery fistulas are rare, and the further development of mitral valvular insufficiency and endocarditis is even more uncommon. We report a case of endocarditis secondary to a congenital coronary artery fistula arising from the right coronary artery and draining into the left ventricle. Vegetations were found on the mitral valve leaflet. The fistula was successfully treated with surgery, and the endocarditis, with antibiotic therapy. Surgical repair is the optimal treatment for coronary artery fistula, even in asymptomatic patients. (J Card Surg 2012;27:714‐715)

Alteration of the Metabolome Profile in Endothelial Cells by Overexpression of miR-143/145.

Communication between endothelial cells (ECs) and smooth muscle cells (SMCs) via miR-143/145 clusters is vital to vascular stability. Previous research demonstrates that miR-143/145 released from ECs can regulate SMC proliferation and migration. In addition, a recent study has found that SMCs also have the capability of manipulating EC function via miR-143/145. In the present study, we artificially increased the expression of miR-143/145 in ECs, to mimic a similar change caused by miR-143/145 released by SMCs, and applied untargeted metabolomics analysis, aimed at investigating the consequential effect of miR-143/145 overexpression. Our results showed that miR-143/145 overexpression alters the levels of metabolites involved in energy production, DNA methylation, and oxidative stress. These changed metabolites indicate that metabolic pathways, such as the SAM cycle and TCA cycle, exhibit significant differences from the norm with miR-143/145 overexpression.