Abstract:
:Atrial tissue gene expression profiling may help to determine how differentially expressed genes in the human atrium before cardiopulmonary bypass (CPB) are related to subsequent biologic pathway activation patterns, and whether specific expression profiles are associated with an increased risk for postoperative atrial fibrillation (AF) or altered response to β-blocker (BB) therapy after coronary artery bypass grafting (CABG) surgery. Right atrial appendage (RAA) samples were collected from 45 patients who were receiving perioperative BB treatment, and underwent CABG surgery. The isolated RNA samples were used for microarray gene expression analysis, to identify probes that were expressed differently in patients with and without postoperative AF. Gene expression analysis was performed to identify probes that were expressed differently in patients with and without postoperative AF. Gene set enrichment analysis (GSEA) was performed to determine how sets of genes might be systematically altered in patients with postoperative AF. Of the 45 patients studied, genomic DNA from 42 patients was used for target sequencing of 66 candidate genes potentially associated with AF, and 2,144 single-nucleotide polymorphisms (SNPs) were identified. We then performed expression quantitative trait loci (eQTL) analysis to determine the correlation between SNPs identified in the genotyped patients, and RAA expression. Probes that met a false discovery rate<0.25 were selected for eQTL analysis. Of the 17,678 gene expression probes analyzed, 2 probes met our prespecified significance threshold of false discovery rate<0.25. The most significant probe corresponded to vesicular overexpressed in cancer - prosurvival protein 1 gene (VOPP1; 1.83 fold change; P=3.47×10(-7)), and was up-regulated in patients with postoperative AF, whereas the second most significant probe, which corresponded to the LOC389286 gene (0.49 fold change; P=1.54×10(-5)), was down-regulated in patients with postoperative AF. GSEA highlighted the role of VOPP1 in pathways with biologic relevance to myocardial homeostasis, and oxidative stress and redox modulation. Candidate gene eQTL showed a trans-acting association between variants of G protein-coupled receptor kinase 5 gene, previously linked to altered BB response, and high expression of VOPP1. In patients undergoing CABG surgery, RAA gene expression profiling, and pathway and eQTL analysis suggested that VOPP1 plays a novel etiological role in postoperative AF despite perioperative BB therapy.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Kertai MD,Qi W,Li YJ,Lombard FW,Liu Y,Smith MP,Stafford-Smith M,Newman MF,Milano CA,Mathew JP,Podgoreanu MV,Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team.doi
10.1016/j.yjmcc.2016.02.006subject
Has Abstractpub_date
2016-03-01 00:00:00pages
109-15eissn
0022-2828issn
1095-8584pii
S0022-2828(16)30034-7journal_volume
92pub_type
杂志文章abstract::Chemokines are small molecular weight proteins that play important roles in inflammation. Originally described as chemotactic cytokines, chemokines stimulate the influx of leukocytes into specific tissue compartments. These molecules also modulate gene expression in both infiltrating and resident cells to mediate a va...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1503
更新日期:2002-02-01 00:00:00
abstract::Type V and VI adenylyl cyclase mRNAs are the two main cyclase isoforms expressed in the mammalian heart. A recent report has shown that their expression is differentially regulated during ontogenic development, but the accumulation of the two mRNA species and their concentration ratio have not been determined. We thus...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(95)90002-0
更新日期:1995-09-01 00:00:00
abstract::We used three interventions to test critically the theory that ischemic preconditioning is the result of translocation of cytosolic protein kinase C (PKC) into the membranes where it can be activated. If that theory were true then kinase activity should not be necessary during the preconditioning ischemia and thus blo...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1078
更新日期:1994-05-01 00:00:00
abstract::Global ischemia in guinea-pig hearts for 60 to 90 min depressed microsomal and mitochondrial Ca2+ uptake activities. Reperfusion of the 60 min ischemic hearts resulted in incomplete recovery of contractile function and calcium uptake activities of both mitochondrial and microsomal fractions. On the other hand, reperfu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(88)90327-6
更新日期:1988-03-01 00:00:00
abstract:RATIONALE:Truncation mutations in the MYBPC3 gene, encoding for cardiac myosin-binding protein C (MyBP-C), are the leading cause of hypertrophic cardiomyopathy (HCM). Whole heart, fiber and molecular studies demonstrate that MyBP-C is a potent modulator of cardiac contractility, but how these mutations contribute to HC...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.12.003
更新日期:2019-02-01 00:00:00
abstract::Phospholipase D (PLD) plays a central role in receptor-mediated breakdown of choline phospholipids and formation of phosphatidic acid (PA), an important regulator of cardiac function. However, specific mechanisms that regulate myocardial PLD activity remain largely unknown, particularly in the human heart. We hypothes...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2003.11.008
更新日期:2004-02-01 00:00:00
abstract::The effects of adenosine on myocardial substrate utilization were assessed in isolated Langendorff-perfused rat hearts. In unpaced hearts perfused at constant flow with insulin, adenosine inhibited oxidation of both glucose and palmitate with similar dose-dependency, without significant effects on effluent lactate+pyr...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)93153-b
更新日期:1992-02-01 00:00:00
abstract:BACKGROUND:Cardiac troponins are the preferred biomarkers of acute myocardial infarction. Despite superior sensitivity, serial testing of Troponins to identify patients suffering acute coronary syndromes is still required in many cases to overcome limited specificity. Moreover, unstable angina pectoris relies on report...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.04.014
更新日期:2020-04-17 00:00:00
abstract::Left ventricular hypertrophy may lead to heart failure. The transition between hypertrophy and heart failure is, however, incompletely understood. On the cellular level, human heart failure is characterized by alterations in Ca(2+)-cycling proteins and beta-adrenergic receptor density, but the hypertrophied human hear...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1390
更新日期:2001-06-01 00:00:00
abstract::Aging enhances cardiac injury during ischemia and reperfusion compared to the adult heart, including in the Fischer 344 rat model of aging (F344). In interfibrillar cardiac mitochondria obtained from the elderly F344 rat, the rate of oxidative phosphorylation and the activity of electron transport complex III is decre...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.03.007
更新日期:2009-06-01 00:00:00
abstract::The authors have previously resolved four forms of cyclic nucleotide phosphodiesterase (PDE) in neonatal rat cultured cardiomyocytes by use of high-performance liquid chromatography (HPLC) and have shown that the response of the cGMP-stimulated PDE to the effector cGMP was markedly reduced as compared to that of the c...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0207
更新日期:1996-10-01 00:00:00
abstract:BACKGROUND:Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are unknown. We used an experimental approach based upon clinical signs of RVF to delineate functional and biological processes associated with RVF. M...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.11.024
更新日期:2015-02-01 00:00:00
abstract::The metabolism of pantothenic acid (Pa) by cardiac muscle was studied in normal and diabetic rats. Tissue levels of Coenzyme A (CoA) are elevated in the heart during early (6 to 12 h) diabetes, remains at a high level for several days, and then returns to normal or below normal levels. The increase in total tissue CoA...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90605-6
更新日期:1989-07-01 00:00:00
abstract::The aim of the present study was to investigate whether or not alterations of Gs alpha can be detected with cholera toxin-induced ADP-ribosylation in myocardial membranes from patients with heart failure. Therefore, Gs alpha was radiolabeled by cholera toxin-catalzyed (32P)ADP-ribosylation with (32P)NAD as substrate. ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(90)90973-6
更新日期:1990-01-01 00:00:00
abstract::Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF)...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0772
更新日期:1998-10-01 00:00:00
abstract::We have compared and contrasted the actions of (-)isoproterenol and (+/-) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]p (guanosine-5'-(beta, gamma imino) triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate ra...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(85)80025-0
更新日期:1985-06-01 00:00:00
abstract::We have identified in soluble extracts of rat heart, a 500 000 dalton sulfhydryl-dependent protease which degrades globin and casein to acid-soluble peptides at an alkaline pH optimum. This enzyme was purified more than 1700-fold with respect to the postmicrosomal supernatant. On the basis of various catalytic and bio...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(83)90304-8
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND:The ability to recapitulate mature adult phenotypes is critical to the development of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) as models of disease. The present study examines the characteristics of the transient outward current (Ito) and its contribution to the hiPSC-CM action p...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.03.014
更新日期:2013-07-01 00:00:00
abstract::Pro-inflammatory cytokines are released in septic shock and impair cardiac function via the Jak-STAT pathway. It is well known that sympathetic stimulation leads to coupling of the β-adrenergic receptor/Gs/adenylyl cyclase, a membrane-bound enzyme that catalyzes the conversion of ATP to cAMP, thereby stimulating prote...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.05.014
更新日期:2017-07-01 00:00:00
abstract::Gender has recently been implicated as an important modulator of cardiovascular disease. However, it is not known how gender may specifically influence the Ca2+-handling deficits that characterize the depressed cardiac contractility of human heart failure. To elucidate the contributory role of gender to sarcoplasmic r...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1394
更新日期:2001-07-01 00:00:00
abstract::Attenuation of excessive rates of myocardial glycolysis limits proton production and Ca(2+) overload during reperfusion and improves recovery of post-ischemic left ventricular (LV) function. In order to elucidate mechanisms underlying glycolytic inhibition by adenosine (ADO), this study tested the hypothesis that the ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.03.014
更新日期:2012-06-01 00:00:00
abstract::The length-dependence of myofilament Ca(2+) sensitivity is considered to be an important component of the steep force-length relationship in cardiac muscle (Frank-Starling relation). Recent studies suggest that Ca(2+) sensitivity is a function of the number of strong-binding cross-bridge interactions formed at a given...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1999.1043
更新日期:1999-12-01 00:00:00
abstract::The present study was undertaken to assess whether [32P]uptake and autoradiography could be used as an indicator of regional myocardial oxygen consumption. Rat hearts were perfused in the Langendorff mode with medium containing [32P]orthophosphate (32Pi) and the incorporation of label into ATP, perchloric acid-insolub...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1035
更新日期:1993-03-01 00:00:00
abstract::Although it is generally accepted that actin and myosin isoforms adapt to their functional requirements, the sequence of expression of these proteins in hearts developing abnormally is unknown. In the chick embryo it is possible to change various aspects of heart development without direct manipulation of the cardiova...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(90)91035-6
更新日期:1990-09-01 00:00:00
abstract::Efficacy of intravenous administration of mesenchymal stromal cells (MSCs) for myocardial infarction (MI) is limited by low cell retention in the damaged myocardium. Previous studies indicated that remote ischemic conditioning could protect against ischemia-reperfusion-induced injury by release of various cytokines in...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.12.016
更新日期:2013-03-01 00:00:00
abstract::It is still a matter of debate, whether decreased protein expression of SERCA 2a and phospholamban (PLB), or alterations in the phosphorylation state of PLB are responsible for the reduced SERCA 2a function in failing human myocardium. Thus, in membrane preparations from patients with terminal heart failure due to idi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0897
更新日期:1999-03-01 00:00:00
abstract::This report examines the blocking effects that several antiarrhythmic drugs have on rapid upstroke velocities of action potentials recorded from guinea-pig papillary muscle. A mathematical analysis is developed, that measures an effective "blocking rate' that acts during the action potential with the purpose being to ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(83)90334-6
更新日期:1983-11-01 00:00:00
abstract::Elevation of intracellular cAMP concentration has numerous vascular protective effects that are in part mediated via actin cytoskeleton-remodelling and subsequent regulation of gene expression. However, the mechanisms are incompletely understood. Here we investigated whether cAMP-induced actin-cytoskeleton remodelling...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.11.012
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitud...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2020.08.008
更新日期:2020-10-01 00:00:00
abstract::The interaction of verapamil and other phenylalkylamine calcium channel blockers with the 1,4-dihydropyridine receptor was examined. Studies characterizing the interaction and relationship between calcium channel blocking potency and binding affinity were performed in rat myocardium. The 1,4-dihydropyridines, nifedipi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80010-4
更新日期:1986-09-01 00:00:00