Diagnostic value of circulating microRNA-19b in heart failure.

OBJECTIVE: For differentiating heart failure (HF) with preserved ejection fraction (HFpEF) from HF with reduced EF (HFrEF), N-terminal prohormone brain natriuretic peptide (NT-proBNP) is less accurate. Decreased expression of microRNA-19b (miR-19b) is associated with increased cardiac-fibrosis. We aim to evaluate the value of miR-19b in diagnosing HFrEF patients. METHOD: We included 200 HF patients and 100 healthy controls. Intergroup comparisons of miR-19b were made and correlation between miR-19b and NT-proBNP was analysed. Diagnostic values of NT-proBNP and miR-19b for HF patients versus controls and HFrEF versus HFpEF were obtained by ROC analysis and described by area under curve (AUC), sensitivity and specificity. RESULTS: HFrEF patients (0.87, 95% CI 0.37-1.45) had significantly lower miR-19b level than HFpEF group (1.32, 95% CI 0.63-2.51) and the controls (1.82, 95% CI 0.37-1.45) (both P < .001). There was a remarkable negative correlation between miR-19b and NT-proBNP (P < .001). The additional use of miR-19b did not improve the accuracy of NT-proBNP alone in diagnosing HF patients from the controls (both AUC = 0.98, 95%CI 0.97-0.99). However, as for distinguishing the HFpEF from HFrEF, miR-19b and NT-proBNP yielded a significantly higher AUC than NT-proBNP alone (0.85, 95% CI 0.80-0.90 vs. 0.66, 95% CI 0.58-0.74) (P < .001), and the sensitivity for diagnosing HFrEF was raised from 58% to 77% and the specificity from 75% to 79%. CONCLUSIONS: On top of NT-proBNP, miR-19b added the value in diagnosing HFrEF. But in view of satisfactory accuracy of NT-proBNP in predicting HF from the healthy volunteers, miR-19b did not provide incremental value.

Intracoronary infusion of bone marrow-derived mononuclear cells contributes to longstanding improvements of left ventricular performance and remodelling after acute myocardial infarction: a meta-analysis.

BACKGROUND: Conflicting results exist now on the sustained effects of intracoronary bone marrow-derived mononuclear cells (BMMNCs) infusion in patients with acute myocardial infarction (AMI). METHODS: Systematical literature search of PubMed, ISI Web of Science, and Cochrane databases was conducted. We included the randomised controlled trials with at least 12-month follow-up data for AMI patients receiving primary percutaneous coronary intervention in addition to intracoronary BMMNCs transfer or not (the control). Summary statistics were calculated using random-effects models. RESULTS: A total of 10 trials with 757 patients were available for analysis. The pooled statistics showed intracoronary administration of BMMNCs significantly improved post-infarction left ventricular ejection fraction (weight mean differences [WMD]=4.04%, 95% confidence intervals [CI], 3.01-5.07%; p<0.01), and attenuated the enlargement of left ventricular end-diastolic volume (WMD=-6.13 ml, 95%CI, -10.56 ml to -1.69 ml; p=0.007) as well as infarct size (WMD=-2.47%, 95%CI, -3.79% to -1.15%; p=0.0002). However, for the major adverse clinical events (MACEs), there appeared to be neutral results (between-group differences of p>0.10). CONCLUSIONS: Intracoronary BMMNCs infusion leads to longstanding and moderate improvements of post-infarction left ventricular performance as well as remodelling. Meanwhile, the procedure did not increase the risk of MACEs.

Potential candidate genes for alveolar hypoxia identified by transcriptome network analysis.

BACKGROUND. Alveolar hypoxia is an important condition related to many disorders such as chronic pulmonary hypertension, pulmonary vasoconstriction, and pulmonary vascular remodeling. The aim of present study was to disclose the biological response and the potential transcriptome networks regulating the hypoxia response in the lungs. MATERIALS AND METHODS. In this study, the microarray dataset GSE11341 was used to construct a regulatory network and identify the potential genes related to alveolar hypoxia. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term enrichment analyses were also performed. RESULTS. Hypoxia inducible factor 1 alpha (HIF-1α), peroxisome proliferator-activated receptor gamma (PPARγ), and nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-кB) were to be the hub nodes in the transcriptome network. HIF-1α may regulate potassium voltage-gated channel, shaker-related subfamily, member (5KCNA5), solute carrier family 2 (facilitated glucose transporter), member (1SLC2A1), and heme oxygenase (decycling) 1 (HMOX1) expression through the regulation of membrane potential, glucose metabolism, and anti-inflammation pathways. HMOX-1 mediates signaling pathways that relate to NF-кB. CCND1 (cyclin D1) expression could be regulated by PPARγ and HIF-1α via the cell cycle pathway. In addition, new transcriptional factors and target genes, such as phosphofructokinase (PFKL, liver), aldolase A (ALDOA, fructose-bisphosphate), and trefoil factor 3 (intestinal) (TFF3), were also identified. CONCLUSIONS. Transcriptome network analysis is a helpful method for the identification of the candidate genes in alveolar hypoxia. The KEGG pathway and GO term analysis are beneficial in the prediction of the underlying molecular mechanism of these identified genes in alveolar hypoxia.

A case with cardiac tamponade as the first sign of primary gastric signet-ring cell carcinoma treated with combination therapy.

BACKGROUND: This report presents a rare patient with cardiac tamponade as the first manifestation of primary gastric signet-ring cell carcinoma. CASE REPORT: A 56-year-old woman with emergent dyspnea, anterior chest oppression, and hypotension was diagnosed as having cardiac tamponade due to massive pericardial effusion. The endoscopic examination of the stomach disclosed gastric cancer in the posterior wall of the antrum and the biopsy showed signet-ring cell carcinoma. The gastric cancer was complicated by malignant pericardial effusion and pleural effusion as well as metastasis to the peripheral lymph nodes and bones. The patient was treated with percutaneous pericardiocentesis followed by systemic chemotherapy (oxaliplatin and sequential 5-fluorouracil plus leucovorin). The pericardial effusion gradually disappeared and there was no cardiac tamponade occurrence. The patient has survived more than 6 months so far. CONCLUSIONS: Cardiac tamponade may originate from a primary gastric signet-ring cell carcinoma. Pericardiocentesis followed by systemic chemotherapy may be effective in controlling such advanced gastric signet-ring cell carcinoma.

[Outcome of transcatheter closure of perimembranous ventricular septal defect with modified double-disk occluder device].

OBJECTIVE: To evaluate the efficacy and adverse effects of transcatheter closure of perimembranous ventricular septal defect (pmVSD) with modified double-disk occluder device (MDVO). METHODS: Clinical data including clinical examination, electrocardiography daily after the procedure for a week, chest-X-rays and TTE before discharge and at 3-5 days after the procedure were analyzed from 604 patients underwent percutaneous closure of a pmVSD with MDVO at our department between December 2001 and December 2008. RESULTS: Procedure was successful in 576 out of 604 patients (95.4%) and 583 VSD occluders were placed. Endocarditis, thromboembolism, or deaths were not observed after procedure. Conduction block occurred in 81 patients (56 RBBB, 14 LBBB) and transient nonparoxysmal ventricular tachycardia in 31 patients after the procedure. Complete heart block occurred in 11 patients, 9 of them recovered in 3 weeks, permanent pacemaker was implanted in 2 patients (one had transient III degrees AVB before the procedure, the other underwent simultaneous closure of ventricular septal defect and atrial septal defect). Trivial/small residual shunts were found in 69 patients (12.0%). The residual shunts disappeared in 31 patients and remained unchanged in 38 patients (6.6%) 7 days after procedures. Aortic regurgitation developed in 5 patients (2 trivial/small, 3 small/moderate), and tricuspid regurgitation was present in 35 patients (32 trivial/small, 3 moderate). Five patients developed haemolysis (device retrieved via catheter in 1 patient due to persistent haemolysis, the other 4 patients recovered 3-14 days post procedure). Pseudoaneurysm of femoral artery occurred in 1 patient, and disappeared by pressure dressing. Device was successfully replaced in 2 patients with either device embolization (n = 1) or device misplacement (n = 1) after device retrieval by catheter. CONCLUSION: It is safe and effective to close congenital perimembranous ventricular septal defect with domestic-made occluder device.

Dysregulation of HULC promotes contrast-induced nephropathy (CIN) via regulating signaling pathway of miRNA-512 and prostaglandin E1 (PGE1).

It has been shown that contrast-induced nephropathy (CIN) can be attenuated by the administration of PGE1. As an enzyme responsible for the production of PGE1, PTGS1 was confirmed in this study as a miR-512 target. Meanwhile, HULC has been identified as a competing endogenous RNA of miR-512. Therefore, in this study, we tested the diagnostic value of HULC and miR-512 in subjects with or without CIN. In addition, we evaluated the regulatory relationship among HULC, miR-512, PTGS1 and PGE1 in vitro. We enrolled 320 patients with coronary heart disease and divided them into a CIN group and a non-CIN group. Subsequently, we detected the differential expression of miR-512, HULC and PGE1 in the two groups. We also used a dual luciferase reporter assay to evaluate the regulatory relationship among HULC, miR-512, PTGS1 and PGE1 in THP-1 cells. In patients with CIN, the expression levels of HULC and PGE1 were lower, but the expression level of miR-512 was higher. MiR-512 could directly bind to and negatively regulate the expression of PTGS1 and HULC. The expression of HULC was positively correlated with the expression of PTGS1 and PGE1, while negatively correlated with the expression of miR-512. The findings of this study demonstrated that deregulation of lncRNA-HULC/miR-512/PTGS1/PGE1 might be involved in the pathogenesis of CIN.

Identification and functional analysis of a novel PRKAG2 mutation responsible for Chinese PRKAG2 cardiac syndrome reveal an important role of non-CBS domains in regulating the AMPK pathway.

BACKGROUND: PRKAG2 gene encodes the γ2 regulatory subunit of AMP-activated protein kinase (AMPK) that acts as a sensor of cellular energy status, and its germline mutations are responsible for PRKAG2 cardiac syndrome (PCS). The majority of missense mutations of cystathionine beta-synthase (CBS) domains found in PCS impair the binding activity of PRKAG2 to adenosine derivatives, and therefore lead to PRKAG2 function impairment and AMPK activity alteration, resulting in a familial syndrome of ventricular preexcitation, conduction defects, and cardiac hypertrophy. However, it is unclear about the PRKAG2 mutation in the non-CBS domain. Here, a Chinese family exhibiting the cardiac syndrome associated with a novel heterozygous PRKAG2 mutation (Gly100Ser) mapped to exon 3 encoding a non-CBS domain is described and the function of this novel mutation was investigated in vitro. METHODS: The PRKAG2 G100S and R302Q mutations were constructed by a two-step polymerase chain reaction and then transfected into CCL13 cells by lentivirus vectors. Wild-type PRKAG2 gene transfection was used as a negative control. PRKAG2 expression was determined by Western blot. Immunofluorescence was used to localize the intracellular PRKAG2 proteins. MTT assay was performed to explore the effect of mutations on cell proliferation. Periodic acid-Schiff staining was used for detecting glycogen accumulation. AMPK concentration was measured with enzyme-linked immunosorbent assay. RESULTS: Our results showed neither intracellular localization of PRKAG2 nor cell growth was altered. In contrast, PRKAG2 protein expression levels were significantly reduced by this mutation. Furthermore, PRKAG2-mediated activity of AMPK was attenuated, resulting in glycogen metabolism dysregulation. These findings revealed that non-CBS domains of PRKAG2 were essential to the regulation of AMPK activity, similar to CBS. CONCLUSIONS: Our study ascribes a crucial regulatory role to the novel PRKAG2 G100S mutation, and reiterates that PCS occurs as a consequence of AMPK signaling abnormality caused by PRKAG2 gene mutations.

Plasma ghrelin and obestatin levels are increased in spontaneously hypertensive rats.

Obestatin, encoded by the same gene as ghrelin, was first described as a physiological opponent of ghrelin. We investigated fasting plasma ghrelin and obestatin levels in spontaneously hypertensive rats and Wistar-Kyoto rats. We found that ghrelin levels, obestatin levels and the ratio of ghrelin to obestatin were significantly higher in spontaneously hypertensive rats than Wistar-Kyoto rats. Systolic blood pressure and diastolic blood pressure were positively correlated; however, heart period and baroreflex sensitivity were negatively correlated with ghrelin levels. Systolic blood pressure was positively correlated, whereas baroreflex sensitivity was negatively correlated with obestatin levels. In addition, systolic blood pressure was a significantly independent variable of ghrelin levels, obestatin levels, and the ghrelin to obestatin ratio in a multiple regression analysis. Our data suggests that there is a disturbance of ghrelin and obestatin in the circulation of spontaneously hypertensive rats and the ghrelin/obestatin system might play a role in blood pressure regulation.