Expressing an inhibitor of PLCβ1b sustains contractile function following pressure overload

Journal of Molecular and Cellular Cardiology
David R GrubbElizabeth A Woodcock

Abstract

The activity of phospholipase Cβ1b (PLCβ1b) is selectively elevated in failing myocardium and cardiac expression of PLCβ1b causes contractile dysfunction. PLCβ1b can be selectively inhibited by expressing a peptide inhibitor that prevents sarcolemmal localization. The inhibitory peptide, PLCβ1b-CT was expressed in heart from a mini-gene using adeno-associated virus (rAAV6-PLCβ1b-CT). rAAV6-PLCβ1b-CT, or blank virus, was delivered IV (4×10(9)vg/g body weight) and trans-aortic-constriction (TAC) or sham-operation was performed 8weeks later. Expression of PLCβ1b-CT prevented the loss of contractile function, eliminated lung congestion and improved survival following TAC with either a 'moderate' or 'severe' pressure gradient. Hypertrophy was attenuated but not eliminated. Expression of the PLCβ1b-CT peptide 2-3weeks after TAC reduced contractile dysfunction and lung congestion, without limiting hypertrophy. PLCβ1b inhibition ameliorates pathological responses following acute pressure overload. The targeting of PLCβ1b to the sarcolemma provides the basis for the development of a new class of inotropic agent.

References

Apr 6, 1999·Trends in Cardiovascular Medicine·G W Dorn, J H Brown
Mar 29, 2001·Journal of Molecular and Cellular Cardiology·A R Marks
Jan 24, 2002·Nature·J A Towbin, N E Bowles
Jul 27, 2004·Nature Medicine·Paul GregorevicJeffrey S Chamberlain
Nov 13, 2004·Circulation Research·Faisal SyedGerald W Dorn
Dec 1, 1994·Trends in Endocrinology and Metabolism : TEM·J A Bristol, S G Rhee
Sep 5, 2009·Journal of Molecular and Cellular Cardiology·Elizabeth A WoodcockAnthony M Dart
Feb 6, 2010·Circulation Research·Karin R Sipido, Peter Vangheluwe
Oct 13, 2010·Journal of Molecular and Cellular Cardiology·Qinghang Liu, Jeffery D Molkentin
Jan 27, 2011·The Journal of Biological Chemistry·Ryan R KleinDhiren R Thakker
Jan 3, 2013·The Journal of Clinical Investigation·Andrew R Marks
Aug 31, 2013·Circulation Research·Min Luo, Mark E Anderson
Dec 24, 2013·European Journal of Pharmacology·Mohammad Abrar ShareefCoralie Poizat
Mar 19, 2014·Journal of Molecular and Cellular Cardiology·Katherine B SchuetzeCarlin S Long
Jul 8, 2014·Lancet·Christian T RuffElliott M Antman
Dec 3, 2014·Journal of Molecular and Cellular Cardiology·Kobra HaghighiEvangelia G Kranias
Apr 11, 2015·Circulation Research·Robert C LyonFarah Sheikh
Apr 26, 2015·Biochemical and Biophysical Research Communications·David R GrubbElizabeth A Woodcock
Apr 29, 2015·Journal of Molecular and Cellular Cardiology·David R GrubbElizabeth A Woodcock
Jul 15, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Thomas Moore-MorrisSylvia M Evans

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