Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization
Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene (sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant...
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| Published in | Circulation (New York, N.Y.) Vol. 147; no. 10; pp. 824 - 840 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Lippincott Williams & Wilkins
07.03.2023
American Heart Association |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene
(sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant in the cardiac transcription factor
(T-box transcription factor 5) and no
variant.
We generated induced pluripotent stem cells (iPSCs) from 2 members of a family carrying TBX5-G145R and diagnosed with Brugada syndrome. After differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), electrophysiologic characteristics were assessed by voltage- and current-clamp experiments (n=9 to 21 cells per group) and transcriptional differences by RNA sequencing (n=3 samples per group), and compared with iPSC-CMs in which G145R was corrected by CRISPR/Cas9 approaches. The role of platelet-derived growth factor (PDGF)/phosphoinositide 3-kinase (PI3K) pathway was elucidated by small molecule perturbation. The rate-corrected QT (QTc) interval association with serum PDGF was tested in the Framingham Heart Study cohort (n=1893 individuals).
TBX5-G145R reduced transcriptional activity and caused multiple electrophysiologic abnormalities, including decreased peak and enhanced "late" cardiac sodium current (I
), which were entirely corrected by editing G145R to wild-type. Transcriptional profiling and functional assays in genome-unedited and -edited iPSC-CMs showed direct
down-regulation caused decreased peak I
, and that reduced PDGF receptor (
[platelet-derived growth factor receptor α]) expression and blunted signal transduction to PI3K was implicated in enhanced late I
. Tbx5 regulation of the PDGF axis increased arrhythmia risk due to disruption of PDGF signaling and was conserved in murine model systems. PDGF receptor blockade markedly prolonged normal iPSC-CM action potentials and plasma levels of PDGF in the Framingham Heart Study were inversely correlated with the QTc interval (
<0.001).
These results not only establish decreased
transcription by the
variant as a cause of BrS, but also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor-mediated PI3K signaling. |
|---|---|
| AbstractList | Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene
(sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant in the cardiac transcription factor
(T-box transcription factor 5) and no
variant.
We generated induced pluripotent stem cells (iPSCs) from 2 members of a family carrying TBX5-G145R and diagnosed with Brugada syndrome. After differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), electrophysiologic characteristics were assessed by voltage- and current-clamp experiments (n=9 to 21 cells per group) and transcriptional differences by RNA sequencing (n=3 samples per group), and compared with iPSC-CMs in which G145R was corrected by CRISPR/Cas9 approaches. The role of platelet-derived growth factor (PDGF)/phosphoinositide 3-kinase (PI3K) pathway was elucidated by small molecule perturbation. The rate-corrected QT (QTc) interval association with serum PDGF was tested in the Framingham Heart Study cohort (n=1893 individuals).
TBX5-G145R reduced transcriptional activity and caused multiple electrophysiologic abnormalities, including decreased peak and enhanced "late" cardiac sodium current (I
), which were entirely corrected by editing G145R to wild-type. Transcriptional profiling and functional assays in genome-unedited and -edited iPSC-CMs showed direct
down-regulation caused decreased peak I
, and that reduced PDGF receptor (
[platelet-derived growth factor receptor α]) expression and blunted signal transduction to PI3K was implicated in enhanced late I
. Tbx5 regulation of the PDGF axis increased arrhythmia risk due to disruption of PDGF signaling and was conserved in murine model systems. PDGF receptor blockade markedly prolonged normal iPSC-CM action potentials and plasma levels of PDGF in the Framingham Heart Study were inversely correlated with the QTc interval (
<0.001).
These results not only establish decreased
transcription by the
variant as a cause of BrS, but also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor-mediated PI3K signaling. BACKGROUND: Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene SCN5A (sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant in the cardiac transcription factor TBX5 (T-box transcription factor 5) and no SCN5A variant. METHODS: We generated induced pluripotent stem cells (iPSCs) from 2 members of a family carrying TBX5-G145R and diagnosed with Brugada syndrome. After differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), electrophysiologic characteristics were assessed by voltage- and current-clamp experiments (n=9 to 21 cells per group) and transcriptional differences by RNA sequencing (n=3 samples per group), and compared with iPSC-CMs in which G145R was corrected by CRISPR/Cas9 approaches. The role of platelet-derived growth factor (PDGF)/phosphoinositide 3-kinase (PI3K) pathway was elucidated by small molecule perturbation. The corrected QT (QTc) interval association with serum PDGF was tested in the Framingham Heart Study cohort (n=1893 individuals). RESULTS: TBX5-G145R reduced transcriptional activity and caused multiple electrophysiologic abnormalities, including decreased peak and enhanced “late” cardiac sodium current (I Na ), which were entirely corrected by editing G145R to wild-type. Transcriptional profiling and functional assays in genome-unedited and -edited iPSC-CMs showed direct SCN5A down-regulation caused decreased peak I Na , and that reduced PDGF receptor ( PDGFRA [platelet-derived growth factor receptor α]) expression and blunted signal transduction to PI3K was implicated in enhanced late I Na . Tbx5 regulation of the PDGF axis and disruption of PDGF signaling, which causes arrhythmia risk, were both conserved in murine model systems. The PDGF receptor blockade markedly prolonged normal iPSC-CM action potentials and plasma levels of PDGF in the Framingham Heart Study were inversely correlated with the QTc interval ( P <0.001). CONCLUSIONS: These results not only establish decreased SCN5A transcription by the TBX5 variant as a cause of BrS, but also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor–mediated PI3K signaling. Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene SCN5A (sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant in the cardiac transcription factor TBX5 (T-box transcription factor 5) and no SCN5A variant.BACKGROUNDBrugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene SCN5A (sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant in the cardiac transcription factor TBX5 (T-box transcription factor 5) and no SCN5A variant.We generated induced pluripotent stem cells (iPSCs) from 2 members of a family carrying TBX5-G145R and diagnosed with Brugada syndrome. After differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), electrophysiologic characteristics were assessed by voltage- and current-clamp experiments (n=9 to 21 cells per group) and transcriptional differences by RNA sequencing (n=3 samples per group), and compared with iPSC-CMs in which G145R was corrected by CRISPR/Cas9 approaches. The role of platelet-derived growth factor (PDGF)/phosphoinositide 3-kinase (PI3K) pathway was elucidated by small molecule perturbation. The rate-corrected QT (QTc) interval association with serum PDGF was tested in the Framingham Heart Study cohort (n=1893 individuals).METHODSWe generated induced pluripotent stem cells (iPSCs) from 2 members of a family carrying TBX5-G145R and diagnosed with Brugada syndrome. After differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), electrophysiologic characteristics were assessed by voltage- and current-clamp experiments (n=9 to 21 cells per group) and transcriptional differences by RNA sequencing (n=3 samples per group), and compared with iPSC-CMs in which G145R was corrected by CRISPR/Cas9 approaches. The role of platelet-derived growth factor (PDGF)/phosphoinositide 3-kinase (PI3K) pathway was elucidated by small molecule perturbation. The rate-corrected QT (QTc) interval association with serum PDGF was tested in the Framingham Heart Study cohort (n=1893 individuals).TBX5-G145R reduced transcriptional activity and caused multiple electrophysiologic abnormalities, including decreased peak and enhanced "late" cardiac sodium current (INa), which were entirely corrected by editing G145R to wild-type. Transcriptional profiling and functional assays in genome-unedited and -edited iPSC-CMs showed direct SCN5A down-regulation caused decreased peak INa, and that reduced PDGF receptor (PDGFRA [platelet-derived growth factor receptor α]) expression and blunted signal transduction to PI3K was implicated in enhanced late INa. Tbx5 regulation of the PDGF axis increased arrhythmia risk due to disruption of PDGF signaling and was conserved in murine model systems. PDGF receptor blockade markedly prolonged normal iPSC-CM action potentials and plasma levels of PDGF in the Framingham Heart Study were inversely correlated with the QTc interval (P<0.001).RESULTSTBX5-G145R reduced transcriptional activity and caused multiple electrophysiologic abnormalities, including decreased peak and enhanced "late" cardiac sodium current (INa), which were entirely corrected by editing G145R to wild-type. Transcriptional profiling and functional assays in genome-unedited and -edited iPSC-CMs showed direct SCN5A down-regulation caused decreased peak INa, and that reduced PDGF receptor (PDGFRA [platelet-derived growth factor receptor α]) expression and blunted signal transduction to PI3K was implicated in enhanced late INa. Tbx5 regulation of the PDGF axis increased arrhythmia risk due to disruption of PDGF signaling and was conserved in murine model systems. PDGF receptor blockade markedly prolonged normal iPSC-CM action potentials and plasma levels of PDGF in the Framingham Heart Study were inversely correlated with the QTc interval (P<0.001).These results not only establish decreased SCN5A transcription by the TBX5 variant as a cause of BrS, but also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor-mediated PI3K signaling.CONCLUSIONSThese results not only establish decreased SCN5A transcription by the TBX5 variant as a cause of BrS, but also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor-mediated PI3K signaling. |
| Author | Kryshtal, Dmytro O. Vasan, Ramachandran S. Kannankeril, Prince J. Wang, Thomas J. Yang, Tao Shaffer, Christian Petropoulou, Evmorfia Jamshidi, Yalda Moskowitz, Ivan P. Johnson, Amanda N. Roden, Dan M. Glazer, Andrew M. Yang, Qiong York, John D. Wells, Quinn S. Keyes, Michelle J. Behr, Elijah R. Brown, Jonathan D. Hong, Charles C. Blair, Marcia A. Gerszten, Robert E. Knollmann, Bjorn C. Benson, Mark D. Ngo, Debby Kim, Kyungsoo Campbell, Courtney C. Parikh, Shan Bersell, Kevin R. Steimle, Jeffrey D. Sheng, Quanhu Mosley, Jonathan D. Short, Laura Salem, Joe-Elie Hale, Andrew T. |
| AuthorAffiliation | Biochemistry (A.T.H., J.D.Y.), Vanderbilt University, Nashville, TN Department of Medicine, University of Maryland School of Medicine, Baltimore (C.C.H.) Boston University School of Medicine, MA (R.S.V., Q.Y.) Medicine (T.Y., J.D.M., J.D.B., J-E.S., Q.S.W., L.S., M.A.B., C.S., T.J.W., B.C.K., D.M.R.), Vanderbilt University, Nashville, TN Molecular Physiology and Biophysics (A.N.J.), Vanderbilt University, Nashville, TN Departments of Pediatrics, Pathology, and Human Genetics, University of Chicago, IL (J.D.S., I.P.M.) Cardiology Clinical Academic Group, Molecular and Clinical Sciences Institute, St George’s, University of London and St George’s University Hospitals National Health Service Foundation Trust, London, UK (E.P., Y.J.) Cardiovascular Research Center (E.J.B., M.D.B., M.J.K., R.E.G.), Beth Israel Deaconess Hospital, Boston, MA Pediatrics (P.J.K.), Vanderbilt University, Nashville, TN Division of Pulmonary and Cardiovascular Medicine (D.N., R.E.G.), Beth Israel Deaconess Hospital, Bosto |
| AuthorAffiliation_xml | – name: Boston University School of Medicine, MA (R.S.V., Q.Y.) – name: Pediatrics (P.J.K.), Vanderbilt University, Nashville, TN – name: Medicine (T.Y., J.D.M., J.D.B., J-E.S., Q.S.W., L.S., M.A.B., C.S., T.J.W., B.C.K., D.M.R.), Vanderbilt University, Nashville, TN – name: Departments of Pediatrics, Pathology, and Human Genetics, University of Chicago, IL (J.D.S., I.P.M.) – name: Biochemistry (A.T.H., J.D.Y.), Vanderbilt University, Nashville, TN – name: Department of Medicine, University of Maryland School of Medicine, Baltimore (C.C.H.) – name: Division of Pulmonary and Cardiovascular Medicine (D.N., R.E.G.), Beth Israel Deaconess Hospital, Boston, MA – name: Cardiovascular Research Center (E.J.B., M.D.B., M.J.K., R.E.G.), Beth Israel Deaconess Hospital, Boston, MA – name: Departments of Pharmacology (K.R.B., A.M.G., D.O.K., K.K., J-E.S., C.C.C., Q.S.W., S.P., B.C.K., D.M.R.), Vanderbilt University, Nashville, TN – name: Molecular Physiology and Biophysics (A.N.J.), Vanderbilt University, Nashville, TN – name: Cardiology Clinical Academic Group, Molecular and Clinical Sciences Institute, St George’s, University of London and St George’s University Hospitals National Health Service Foundation Trust, London, UK (E.P., Y.J.) |
| Author_xml | – sequence: 1 givenname: Kevin R. surname: Bersell fullname: Bersell, Kevin R. organization: Departments of Pharmacology (K.R.B., A.M.G., D.O.K., K.K., J-E.S., C.C.C., Q.S.W., S.P., B.C.K., D.M.R.), Vanderbilt University, Nashville, TN – sequence: 2 givenname: Tao surname: Yang fullname: Yang, Tao organization: Medicine (T.Y., J.D.M., J.D.B., J-E.S., Q.S.W., L.S., M.A.B., C.S., T.J.W., B.C.K., D.M.R.), Vanderbilt University, Nashville, TN – sequence: 3 givenname: Jonathan D. surname: Mosley fullname: Mosley, Jonathan D. organization: Departments of Pharmacology (K.R.B., A.M.G., D.O.K., K.K., J-E.S., C.C.C., Q.S.W., S.P., B.C.K., D.M.R.), Vanderbilt University, Nashville, TN – sequence: 4 givenname: Andrew M. surname: Glazer fullname: Glazer, Andrew M. organization: Departments of Pharmacology (K.R.B., A.M.G., D.O.K., K.K., J-E.S., C.C.C., Q.S.W., S.P., B.C.K., D.M.R.), Vanderbilt University, Nashville, TN – sequence: 5 givenname: Andrew T. surname: Hale fullname: Hale, 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| Cites_doi | 10.1093/nar/gkv007 10.1016/j.tcm.2015.05.006 10.1161/CIRCULATIONAHA.118.035070 10.1161/01.cir.86.5.1376 10.1093/bioinformatics/btt656 10.1161/01.cir.89.4.1681 10.1161/CIRCULATIONAHA.119.043132 10.1155/2014/986048 10.1016/0735-1097(92)90253-j 10.1016/s0735-1097(00)00962-1 10.1161/CIRCRESAHA.117.310959 10.1038/nprot.2013.143 10.1016/j.cell.2016.11.033 10.1152/ajpheart.00071.2017 10.1093/bioinformatics/btt703 10.1016/j.hrthm.2013.03.014 10.1126/scitranslmed.3003623 10.1016/j.jacc.2014.04.032 10.1161/CIRCGENETICS.110.959130 10.1016/j.hrthm.2011.02.021 10.1016/j.jacc.2009.10.033 10.1186/1475-925X-10-17 10.1093/cvr/cvv042 10.1016/j.stem.2013.05.016 10.1016/j.hrthm.2010.06.016 10.1124/jpet.117.246157 10.1038/ng.2712 10.1126/science.aaa5458 10.3389/fphar.2013.00078 10.1126/scitranslmed.aaf4891 10.1093/eurheartj/ehv445 10.1111/bph.14223 10.1002/humu.22328 10.1172/JCI73140 10.1177/2211068214562832 10.1161/CIRCULATIONAHA.116.021803 10.1016/j.hrthm.2020.07.038 10.1016/j.hrthm.2011.12.006 10.1038/ncomms7955 10.1161/CIRCEP.111.969972 10.1016/j.bpj.2011.09.060 10.1016/s0092-8674(01)00493-7 10.1111/j.1445-5994.1995.tb00573.x 10.1016/j.hrthm.2010.08.026 10.1016/j.yjmcc.2017.12.002 10.1016/0091-7435(75)90037-7 10.1161/CIRCULATIONAHA.106.646513 10.1016/j.cjca.2011.11.011 10.1093/hmg/10.18.1983 10.1161/CIRCULATIONAHA.106.668392 10.1093/nar/gkaa1106 10.1152/ajpheart.00306.2013 10.1016/0022-0736(88)90096-9 10.1016/j.cardiores.2005.06.027 10.1016/j.hrthm.2020.06.027 10.1172/JCI62613 10.1093/bioinformatics/btp616 10.1038/ng.716 10.1161/CIRCULATIONAHA.113.007765 10.1161/01.cir.97.5.457 10.1016/j.acvd.2016.12.011 10.1161/CIRCEP.110.959619 10.1161/CIRCGENETICS.114.000831 10.1161/01.cir.103.5.670 10.1016/j.clml.2021.09.002 10.1186/gb-2013-14-4-r36 10.1172/JCI87968 10.7554/eLife.41814 10.1016/j.jacc.2012.04.037 10.1371/journal.pone.0015004 10.1161/CIRCULATIONAHA.110.000661 10.1126/sciadv.abk0052 10.1016/j.yjmcc.2004.11.005 10.1093/bioinformatics/bts635 10.1161/CIRCEP.107.748103 10.1073/pnas.96.6.2919 10.1093/europace/euv078 10.1016/j.jelectrocard.2006.05.030 10.1161/CIRCGENETICS.113.000292 10.1136/openhrt-2013-000031 10.1172/JCI33891 10.1504/ijcbdd.2015.072082 10.1161/01.res.87.10.910 10.1161/01.CIR.0000145162.64183.C8 10.1093/cvr/cvab045 10.1093/bioinformatics/btr174 10.3389/fphys.2013.00179 10.1172/JCI39942 10.1126/scitranslmed.aaf2584 10.1038/s41586-019-1406-x 10.1161/CIRCULATIONAHA.107.703330 10.1016/j.jacc.2016.07.779 10.1007/978-1-0716-0167-9_7 10.1053/euhj.1997.0865 10.1016/j.devcel.2016.01.009 10.1111/bph.13563 10.1161/CIRCEP.117.005282 10.2337/db13-0420 10.1016/j.ijcard.2014.04.133 10.1016/j.cardiores.2004.09.021 10.1371/journal.pone.0054131 10.1038/srep04670 10.1128/MCB.01923-08 10.1161/01.CIR.0000139333.83620.5D 10.1038/32675 |
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| References | e_1_3_3_96_2 e_1_3_3_50_2 e_1_3_3_77_2 e_1_3_3_16_2 e_1_3_3_39_2 e_1_3_3_12_2 e_1_3_3_58_2 e_1_3_3_35_2 e_1_3_3_92_2 e_1_3_3_54_2 e_1_3_3_31_2 e_1_3_3_73_2 e_1_3_3_61_2 e_1_3_3_88_2 e_1_3_3_5_2 e_1_3_3_105_2 e_1_3_3_9_2 e_1_3_3_27_2 e_1_3_3_23_2 e_1_3_3_69_2 e_1_3_3_46_2 e_1_3_3_80_2 e_1_3_3_65_2 e_1_3_3_84_2 e_1_3_3_101_2 e_1_3_3_76_2 e_1_3_3_99_2 e_1_3_3_19_2 e_1_3_3_38_2 e_1_3_3_15_2 e_1_3_3_34_2 e_1_3_3_57_2 e_1_3_3_91_2 e_1_3_3_11_2 e_1_3_3_30_2 e_1_3_3_53_2 e_1_3_3_72_2 e_1_3_3_95_2 e_1_3_3_60_2 e_1_3_3_87_2 e_1_3_3_8_2 e_1_3_3_104_2 e_1_3_3_49_2 e_1_3_3_26_2 e_1_3_3_45_2 e_1_3_3_68_2 e_1_3_3_4_2 e_1_3_3_22_2 e_1_3_3_41_2 e_1_3_3_64_2 e_1_3_3_83_2 e_1_3_3_100_2 e_1_3_3_75_2 e_1_3_3_71_2 e_1_3_3_98_2 e_1_3_3_79_2 e_1_3_3_18_2 e_1_3_3_37_2 e_1_3_3_90_2 e_1_3_3_14_2 e_1_3_3_56_2 e_1_3_3_33_2 e_1_3_3_94_2 e_1_3_3_10_2 e_1_3_3_52_2 e_1_3_3_40_2 e_1_3_3_86_2 e_1_3_3_107_2 e_1_3_3_7_2 e_1_3_3_29_2 e_1_3_3_48_2 e_1_3_3_25_2 e_1_3_3_67_2 e_1_3_3_44_2 e_1_3_3_82_2 e_1_3_3_103_2 e_1_3_3_3_2 e_1_3_3_21_2 e_1_3_3_63_2 e_1_3_3_51_2 e_1_3_3_74_2 e_1_3_3_97_2 e_1_3_3_70_2 e_1_3_3_78_2 e_1_3_3_17_2 e_1_3_3_13_2 e_1_3_3_36_2 e_1_3_3_59_2 e_1_3_3_32_2 e_1_3_3_55_2 e_1_3_3_93_2 e_1_3_3_62_2 e_1_3_3_85_2 e_1_3_3_89_2 Yang T HC (e_1_3_3_42_2) 2015; 12 e_1_3_3_6_2 e_1_3_3_106_2 e_1_3_3_28_2 e_1_3_3_24_2 e_1_3_3_47_2 e_1_3_3_2_2 e_1_3_3_20_2 e_1_3_3_43_2 e_1_3_3_66_2 e_1_3_3_81_2 e_1_3_3_102_2 |
| References_xml | – ident: e_1_3_3_18_2 doi: 10.1093/nar/gkv007 – ident: e_1_3_3_25_2 doi: 10.1016/j.tcm.2015.05.006 – ident: e_1_3_3_8_2 doi: 10.1161/CIRCULATIONAHA.118.035070 – ident: e_1_3_3_21_2 doi: 10.1161/01.cir.86.5.1376 – ident: e_1_3_3_76_2 doi: 10.1093/bioinformatics/btt656 – ident: e_1_3_3_22_2 doi: 10.1161/01.cir.89.4.1681 – ident: e_1_3_3_47_2 doi: 10.1161/CIRCULATIONAHA.119.043132 – volume: 12 start-page: S150 year: 2015 ident: e_1_3_3_42_2 article-title: Inhibition of the α-subunit of PI3 kinase increases late sodium current (INa-L) and generates arrhythmias. publication-title: Heart Rhythm – ident: e_1_3_3_77_2 doi: 10.1155/2014/986048 – ident: e_1_3_3_4_2 doi: 10.1016/0735-1097(92)90253-j – ident: e_1_3_3_57_2 doi: 10.1016/s0735-1097(00)00962-1 – ident: e_1_3_3_33_2 doi: 10.1161/CIRCRESAHA.117.310959 – ident: e_1_3_3_66_2 doi: 10.1038/nprot.2013.143 – ident: e_1_3_3_36_2 doi: 10.1016/j.cell.2016.11.033 – ident: e_1_3_3_71_2 doi: 10.1152/ajpheart.00071.2017 – ident: e_1_3_3_82_2 doi: 10.1093/bioinformatics/btt703 – ident: e_1_3_3_53_2 doi: 10.1016/j.hrthm.2013.03.014 – ident: e_1_3_3_39_2 doi: 10.1126/scitranslmed.3003623 – ident: e_1_3_3_107_2 doi: 10.1016/j.jacc.2014.04.032 – ident: e_1_3_3_100_2 doi: 10.1161/CIRCGENETICS.110.959130 – ident: e_1_3_3_102_2 doi: 10.1016/j.hrthm.2011.02.021 – ident: e_1_3_3_67_2 doi: 10.1016/j.jacc.2009.10.033 – ident: e_1_3_3_74_2 doi: 10.1186/1475-925X-10-17 – ident: e_1_3_3_11_2 doi: 10.1093/cvr/cvv042 – ident: e_1_3_3_60_2 doi: 10.1016/j.stem.2013.05.016 – ident: e_1_3_3_99_2 doi: 10.1016/j.hrthm.2010.06.016 – ident: e_1_3_3_43_2 doi: 10.1124/jpet.117.246157 – ident: e_1_3_3_37_2 doi: 10.1038/ng.2712 – ident: e_1_3_3_61_2 doi: 10.1126/science.aaa5458 – ident: e_1_3_3_23_2 doi: 10.3389/fphar.2013.00078 – ident: e_1_3_3_46_2 doi: 10.1126/scitranslmed.aaf4891 – ident: e_1_3_3_20_2 doi: 10.1093/eurheartj/ehv445 – ident: e_1_3_3_72_2 doi: 10.1111/bph.14223 – ident: e_1_3_3_105_2 doi: 10.1002/humu.22328 – ident: e_1_3_3_34_2 doi: 10.1172/JCI73140 – ident: e_1_3_3_31_2 doi: 10.1177/2211068214562832 – ident: e_1_3_3_84_2 doi: 10.1161/CIRCULATIONAHA.116.021803 – ident: e_1_3_3_59_2 doi: 10.1016/j.hrthm.2020.07.038 – ident: e_1_3_3_97_2 doi: 10.1016/j.hrthm.2011.12.006 – ident: e_1_3_3_3_2 doi: 10.1038/ncomms7955 – ident: e_1_3_3_103_2 doi: 10.1161/CIRCEP.111.969972 – ident: e_1_3_3_30_2 doi: 10.1016/j.bpj.2011.09.060 – ident: e_1_3_3_16_2 doi: 10.1016/s0092-8674(01)00493-7 – ident: e_1_3_3_29_2 doi: 10.1111/j.1445-5994.1995.tb00573.x – ident: e_1_3_3_92_2 doi: 10.1016/j.hrthm.2010.08.026 – ident: e_1_3_3_32_2 doi: 10.1016/j.yjmcc.2017.12.002 – ident: e_1_3_3_83_2 doi: 10.1016/0091-7435(75)90037-7 – ident: e_1_3_3_41_2 doi: 10.1161/CIRCULATIONAHA.106.646513 – ident: e_1_3_3_94_2 doi: 10.1016/j.cjca.2011.11.011 – ident: e_1_3_3_64_2 doi: 10.1093/hmg/10.18.1983 – ident: e_1_3_3_91_2 doi: 10.1161/CIRCULATIONAHA.106.668392 – ident: e_1_3_3_79_2 doi: 10.1093/nar/gkaa1106 – ident: e_1_3_3_50_2 doi: 10.1152/ajpheart.00306.2013 – ident: e_1_3_3_86_2 doi: 10.1016/0022-0736(88)90096-9 – ident: e_1_3_3_98_2 doi: 10.1016/j.cardiores.2005.06.027 – ident: e_1_3_3_38_2 doi: 10.1016/j.hrthm.2020.06.027 – ident: e_1_3_3_12_2 doi: 10.1172/JCI62613 – ident: e_1_3_3_17_2 doi: 10.1093/bioinformatics/btp616 – ident: e_1_3_3_13_2 doi: 10.1038/ng.716 – ident: e_1_3_3_26_2 doi: 10.1161/CIRCULATIONAHA.113.007765 – ident: e_1_3_3_5_2 doi: 10.1161/01.cir.97.5.457 – ident: e_1_3_3_89_2 doi: 10.1016/j.acvd.2016.12.011 – ident: e_1_3_3_101_2 doi: 10.1161/CIRCEP.110.959619 – ident: e_1_3_3_9_2 doi: 10.1161/CIRCGENETICS.114.000831 – ident: e_1_3_3_62_2 doi: 10.1161/01.cir.103.5.670 – ident: e_1_3_3_52_2 doi: 10.1016/j.clml.2021.09.002 – ident: e_1_3_3_80_2 doi: 10.1186/gb-2013-14-4-r36 – ident: e_1_3_3_35_2 doi: 10.1172/JCI87968 – ident: e_1_3_3_45_2 doi: 10.7554/eLife.41814 – ident: e_1_3_3_93_2 doi: 10.1016/j.jacc.2012.04.037 – ident: e_1_3_3_85_2 doi: 10.1371/journal.pone.0015004 – ident: e_1_3_3_68_2 doi: 10.1161/CIRCULATIONAHA.110.000661 – ident: e_1_3_3_54_2 doi: 10.1126/sciadv.abk0052 – ident: e_1_3_3_63_2 doi: 10.1016/j.yjmcc.2004.11.005 – ident: e_1_3_3_75_2 doi: 10.1093/bioinformatics/bts635 – ident: e_1_3_3_96_2 doi: 10.1161/CIRCEP.107.748103 – ident: e_1_3_3_14_2 doi: 10.1073/pnas.96.6.2919 – ident: e_1_3_3_106_2 doi: 10.1093/europace/euv078 – ident: e_1_3_3_88_2 doi: 10.1016/j.jelectrocard.2006.05.030 – ident: e_1_3_3_7_2 doi: 10.1161/CIRCGENETICS.113.000292 – ident: e_1_3_3_19_2 doi: 10.1136/openhrt-2013-000031 – ident: e_1_3_3_95_2 doi: 10.1172/JCI33891 – ident: e_1_3_3_78_2 doi: 10.1504/ijcbdd.2015.072082 – ident: e_1_3_3_70_2 doi: 10.1161/01.res.87.10.910 – ident: e_1_3_3_27_2 doi: 10.1161/01.CIR.0000145162.64183.C8 – ident: e_1_3_3_49_2 doi: 10.1093/cvr/cvab045 – ident: e_1_3_3_81_2 doi: 10.1093/bioinformatics/btr174 – ident: e_1_3_3_6_2 doi: 10.3389/fphys.2013.00179 – ident: e_1_3_3_56_2 doi: 10.1172/JCI39942 – ident: e_1_3_3_51_2 doi: 10.1126/scitranslmed.aaf2584 – ident: e_1_3_3_55_2 doi: 10.1038/s41586-019-1406-x – ident: e_1_3_3_90_2 doi: 10.1161/CIRCULATIONAHA.107.703330 – ident: e_1_3_3_2_2 doi: 10.1016/j.jacc.2016.07.779 – ident: e_1_3_3_40_2 doi: 10.1007/978-1-0716-0167-9_7 – ident: e_1_3_3_58_2 doi: 10.1053/euhj.1997.0865 – ident: e_1_3_3_44_2 doi: 10.1016/j.devcel.2016.01.009 – ident: e_1_3_3_73_2 doi: 10.1111/bph.13563 – ident: e_1_3_3_48_2 doi: 10.1161/CIRCEP.117.005282 – ident: e_1_3_3_24_2 doi: 10.2337/db13-0420 – ident: e_1_3_3_87_2 doi: 10.1016/j.ijcard.2014.04.133 – ident: e_1_3_3_15_2 doi: 10.1016/j.cardiores.2004.09.021 – ident: e_1_3_3_104_2 doi: 10.1371/journal.pone.0054131 – ident: e_1_3_3_28_2 doi: 10.1038/srep04670 – ident: e_1_3_3_65_2 doi: 10.1128/MCB.01923-08 – ident: e_1_3_3_69_2 doi: 10.1161/01.CIR.0000139333.83620.5D – ident: e_1_3_3_10_2 doi: 10.1038/32675 |
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| Snippet | Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene
(sodium voltage-gated channel... Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene SCN5A (sodium voltage-gated... BACKGROUND: Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene SCN5A (sodium... |
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| SubjectTerms | Animals Arrhythmias, Cardiac - genetics Arrhythmias, Cardiac - metabolism Brugada Syndrome Humans Life Sciences Mice Myocytes, Cardiac - metabolism NAV1.5 Voltage-Gated Sodium Channel - genetics NAV1.5 Voltage-Gated Sodium Channel - metabolism Phenotype Phosphatidylinositol 3-Kinases - metabolism Receptors, Platelet-Derived Growth Factor - genetics Receptors, Platelet-Derived Growth Factor - metabolism Sodium - metabolism |
| Title | Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization |
| URI | https://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00003017-202303070-00006 https://www.ncbi.nlm.nih.gov/pubmed/36524479 https://www.proquest.com/docview/2755580672 https://hal.science/hal-04002896 |
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