Targeted SERCA2a gene expression identifies molecular mechanism and therapeutic target for arrhythmogenic cardiac alternans.

Circulation. Arrhythmia and Electrophysiology
Michael J CutlerDavid S Rosenbaum

Abstract

Beat-to-beat alternans of cellular repolarization is closely linked to ventricular arrhythmias in humans. We hypothesized that sarcoplasmic reticulum calcium reuptake by SERCA2a plays a central role in the mechanism of cellular alternans and that increasing SERCA2a gene expression will retard the development of cellular alternans. In vivo gene transfer of a recombinant adenoviral vector with the transgene for SERCA2a (Ad.SERCA2a) was performed in young guinea pigs. Isolated myocytes transduced with Ad.SERCA2a exhibited improved sarcoplasmic reticulum Ca(2+) reuptake (P<0.05) and were markedly resistant to cytosolic calcium alternans (P<0.05) under repetitive constant action potential clamp conditions (ie, when alternation of action potential duration was prevented), proving that sarcoplasmic reticulum Ca(2+) cycling is an important mechanism in the development of cellular alternans. Similarly, SERCA2a overexpression in the intact heart demonstrated significant resistance to alternation of action potential duration when compared with control hearts (heart rate threshold, 484+/-25 bpm versus 396+/-11 bpm, P<0.01), with no change in action potential duration restitution slope. Importantly, SERCA2a overexpression produced a 4-fold ...Continue Reading

References

Jun 1, 1992·Pflügers Archiv : European journal of physiology·B E RobertsonR Z Kozlowski
Aug 1, 1992·Journal of the American College of Cardiology·B Surawicz, C Fisch
Jul 1, 1992·American Journal of Hypertension·W H SheuG M Reaven
Jan 27, 1994·The New England Journal of Medicine·D S RosenbaumR J Cohen
Mar 17, 1999·Circulation·J M PastoreD S Rosenbaum
Dec 10, 1999·Biophysical Journal·E ChudinB Kogan
Jan 11, 2000·Circulation Research·J M Pastore, D S Rosenbaum
Jan 2, 2003·The Journal of Physiology·Federica del Monte, Roger J Hajjar
Feb 26, 2003·Circulation Research·Kenneth R LauritaMichael H Koo
Oct 1, 1954·The American Journal of Physiology·B F HOFFMAN, E E SUCKLING
Oct 11, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Rodolphe P KatraKenneth R Laurita
Oct 29, 2003·Circulation·Mariah L WalkerDavid S Rosenbaum
Jan 31, 2004·Circulation Research·Mary E DíazDavid A Eisner
Mar 16, 2004·Circulation Research·Etienne J PruvotKenneth R Laurita
Mar 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Federica del MonteRoger J Hajjar
Mar 24, 2005·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Yohannes ShiferawAlain Karma
Jul 20, 2005·Journal of Molecular and Cellular Cardiology·Xiaoping WanDavid S Rosenbaum
May 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stephan E LehnartAndrew R Marks
May 27, 2006·Circulation Research·James N WeissZhilin Qu
Nov 23, 2006·Physiology·Donald M Bers

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Citations

Dec 17, 2010·Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing·Gerard J J Boink, Michael R Rosen
Jan 12, 2013·Current Cardiology Reports·Charbel NaimRoger J Hajjar
Jun 8, 2012·Gene Therapy·J-S HulotR J Hajjar
Apr 27, 2012·Gene Therapy·J K Donahue
Oct 24, 2012·Nature Reviews. Cardiology·Changwon KhoRoger J Hajjar
Oct 2, 2009·Chaos·Juan G Restrepo, Alain Karma
Apr 3, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Vyacheslav M ShkrylLothar A Blatter
Jun 5, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Michael Nivala, Zhilin Qu
Mar 3, 2012·Circulation Research·Lisa TilemannRoger J Hajjar
Jun 9, 2012·Circulation Research·Evangelia G Kranias, Roger J Hajjar
Jun 8, 2011·Circulation·Sanjiv M NarayanDavid E Krummen
Jan 3, 2013·The Journal of Clinical Investigation·Roger J Hajjar
Feb 26, 2014·Pflügers Archiv : European journal of physiology·Fadi G Akar, Roger J Hajjar
Nov 30, 2014·The Canadian Journal of Cardiology·Stanley NattelPaul Khairy
Feb 23, 2013·Basic Research in Cardiology·Yukiomi TsujiDobromir Dobrev
Apr 14, 2015·Expert Opinion on Biological Therapy·Lukas J Motloch, Fadi G Akar
Mar 1, 2012·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Danna A SpearsVijay S Chauhan
Jan 17, 2012·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Katja E OdeningGideon Koren
Feb 15, 2011·Trends in Pharmacological Sciences·Michael J CutlerDavid S Rosenbaum
Nov 26, 2010·Journal of Molecular and Cellular Cardiology·Judith K GwathmeyRoger J Hajjar
Aug 11, 2010·Journal of Molecular and Cellular Cardiology·Ian Greener, J Kevin Donahue
Apr 20, 2011·Pacing and Clinical Electrophysiology : PACE·Marc DorenkampMarkus Zabel
Nov 8, 2012·Journal of Cardiovascular Electrophysiology·Gordon F Tomaselli
Jul 22, 2014·Clinical and Experimental Pharmacology & Physiology·Joshua N Edwards, Lothar A Blatter
Jul 22, 2010·Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc·Tuomo Nieminen, Richard L Verrier
Oct 22, 2013·British Journal of Pharmacology·Markus B SikkelAlexander R Lyon
Apr 29, 2015·Nature Reviews. Cardiology·Rossana Bongianino, Silvia G Priori
May 24, 2015·Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing·Thomas H EverettJeffrey E Olgin
Mar 7, 2014·Journal of Zhejiang University. Science. B·Yun-Liang Zang, Ling Xia
Dec 15, 2010·Journal of Molecular and Cellular Cardiology·Rachel C MylesGodfrey L Smith
Oct 30, 2012·Journal of Molecular and Cellular Cardiology·Zhilin QuJames N Weiss
May 12, 2016·Heart Failure Reviews·George H KunkelSuresh C Tyagi
May 25, 2016·Heart Rhythm : the Official Journal of the Heart Rhythm Society·J D BayerN A Trayanova
Oct 30, 2016·European Journal of Pharmacology·Patrick LugenbielDierk Thomas
Oct 21, 2016·Scientific Reports·Zhilin QuMichael Nivala
Feb 8, 2018·Frontiers in Physiology·James WinterMichael J Shattock
Aug 22, 2013·Journal of the American Heart Association·Julie A Wolfram, J Kevin Donahue
Dec 11, 2014·Circulation. Arrhythmia and Electrophysiology·Bradley N PlummerKenneth R Laurita
Jun 6, 2015·Circulation Research·Stefan WagnerDonald M Bers

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