title: Atrioventricular Node Dysfunction and Ion Channel Transcriptome in Pulmonary Hypertension.
abstract: Heart block is associated with pulmonary hypertension, and the aim of the study was to test the hypothesis that the heart block is the result of a change in the ion channel transcriptome of the atrioventricular (AV) node.
  
  
  
  The most commonly used animal model of pulmonary hypertension, the monocrotaline-injected rat, was used. The functional consequences of monocrotaline injection were determined by echocardiography, ECG recording, and electrophysiological experiments on the Langendorff-perfused heart and isolated AV node. The ion channel transcriptome was measured by quantitative PCR, and biophysically detailed computer modeling was used to explore the changes observed. After monocrotaline injection, echocardiography revealed the pattern of pulmonary artery blood flow characteristic of pulmonary hypertension and right-sided hypertrophy and failure; the Langendorff-perfused heart and isolated AV node revealed dysfunction of the AV node (eg, 50% incidence of heart block in isolated AV node); and quantitative PCR revealed a widespread downregulation of ion channel and related genes in the AV node (eg, >50% downregulation of Cav1.2/3 and HCN1/2/4 channels). Computer modeling predicted that the changes in the transcriptome if translated into protein and function would result in heart block.
  
  
  
  Pulmonary hypertension results in a derangement of the ion channel transcriptome in the AV node, and this is the likely cause of AV node dysfunction in this disease.
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Ian P
authors.initials: IP
authors.lastname: Temple
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Sunil Jit R J
authors.initials: SJ
authors.lastname: Logantha
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Mais
authors.initials: M
authors.lastname: Absi
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Pervolaraki
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Joseph
authors.initials: J
authors.lastname: Yanni
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Atkinson
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Maria
authors.initials: M
authors.lastname: Petkova
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Quigley
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Simon
authors.initials: S
authors.lastname: Castro
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Mark
authors.initials: M
authors.lastname: Drinkhill
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Heiko
authors.initials: H
authors.lastname: Schneider
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Oliver
authors.initials: O
authors.lastname: Monfredi
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cartwright
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Min
authors.initials: M
authors.lastname: Zi
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Tomoko T
authors.initials: TT
authors.lastname: Yamanushi
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Vaikom S
authors.initials: VS
authors.lastname: Mahadevan
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Alison M
authors.initials: AM
authors.lastname: Gurney
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Ed
authors.initials: E
authors.lastname: White
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Henggui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: George
authors.initials: G
authors.lastname: Hart
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.). mark.boyett@manchester.ac.uk.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Boyett
authors.affiliation: From the Institute of Cardiovascular Sciences (I.P.T., S.J.R.J.L., M.A., Y.Z., J.Y., A.A., M.P., G.M.Q., H.S., O.M., E.C., M.Z., A.M.G., G.H., M.R.B., H.D.) and School of Physics and Astronomy (S.C., H.Z.), University of Manchester, United Kingdom; School of Biomedical Sciences, University of Leeds, United Kingdom (E.P., M.D., E.W.); Kagawa Prefectural College of Health Sciences, Takamatsu, Japan (T.T.Y.); and Department of Medicine, University of California, San Francisco (V.S.M.).
authors.forename: Halina
authors.initials: H
authors.lastname: Dobrzynski
mesh_terms: D000818:Animals; D001283:Atrioventricular Node / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004452:Echocardiography; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D006327:Heart Block / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D059467:Transcriptome
chemical_list: D007473:Ion Channels; D016686:Monocrotaline
keywords: atrioventricular node; echocardiography; heart block; ion channels; transcriptome