Elevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines

American Journal of Physiology. Heart and Circulatory Physiology
Sarah A ClayMaike Krenz

Abstract

Noonan syndrome with multiple lentigines (NSML) is primarily caused by mutations in the nonreceptor protein tyrosine phosphatase SHP2 and associated with congenital heart disease in the form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Our goal was to elucidate the cellular mechanisms underlying the development of HCM caused by the Q510E mutation in SHP2. NSML patients carrying this mutation suffer from a particularly severe form of HCM. Drawing parallels to other, more common forms of HCM, we hypothesized that altered Ca(2+) homeostasis and/or sarcomeric mechanical properties play key roles in the pathomechanism. We used transgenic mice with cardiomyocyte-specific expression of Q510E-SHP2 starting before birth. Mice develop neonatal onset HCM with increased ejection fraction and fractional shortening at 4-6 wk of age. To assess Ca(2+) handling, isolated cardiomyocytes were loaded with fluo-4. Q510E-SHP2 expression increased Ca(2+) transient amplitudes during excitation-contraction coupling and increased sarcoplasmic reticulum Ca(2+) content concurrent with increased expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase. In skinned cardiomyocyte preparations from Q510E-SHP2 mice, force-velocity relation...Continue Reading

References

Jun 1, 1986·The Journal of Cell Biology·J M SangerJ W Sanger
Aug 6, 1971·Biochimica Et Biophysica Acta·R J SolaroF N Briggs
Oct 1, 1995·Circulation·E D WigleW G Williams
May 1, 1995·The American Journal of Physiology·J W BassaniD M Bers
Mar 1, 1996·Circulation Research·J PalermoJ Robbins
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 12, 2002·American Journal of Human Genetics·Maria Cristina DigilioBruno Dallapiccola
Aug 6, 2002·Journal of Medical Genetics·E LegiusJ-P Fryns
Sep 19, 2002·Proceedings of the National Academy of Sciences of the United States of America·Gianluigi CondorelliJohn Ross
Mar 11, 2003·The Journal of Biological Chemistry·Maike KrenzJeffrey Robbins
Jun 27, 2003·Trends in Biochemical Sciences·Benjamin G NeelLily Pao
Sep 18, 2003·The Journal of Biological Chemistry·Young-Kwon KimStephen F Vatner
Apr 16, 2004·American Journal of Physiology. Cell Physiology·Aaron C Hinken, Kerry S McDonald
May 4, 2004·Journal of Medical Genetics·A SarkozyB Dallapiccola
Apr 6, 2005·Cell Motility and the Cytoskeleton·Jushuo WangJoseph W Sanger
Mar 9, 2006·American Journal of Medical Genetics. Part a·M Cristina DigilioBruno Dallapiccola
Aug 19, 2007·The American Journal of Cardiology·Giuseppe LimongelliRaffaele Calabro
Feb 5, 2008·American Journal of Medical Genetics. Part a·Giuseppe LimongelliRaffaele Calabrò
Mar 3, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Laurin M Hanft, Kerry S McDonald
Mar 25, 2009·The Journal of Cell Biology·Daniele CatalucciGianluigi Condorelli
May 7, 2009·European Journal of Medical Genetics·Monika KoudovaMartin Zenker
Feb 18, 2010·Circulation. Arrhythmia and Electrophysiology·Christian van der WerfArthur A M Wilde
Jan 12, 2011·Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance·Iris K RüsselAlbert C van Rossum
Feb 23, 2011·The Journal of Clinical Investigation·Talita M MarinMaria I Kontaridis
Sep 20, 2011·The American Journal of Cardiology·Jose A Urbano MoralNatesa G Pandian
Oct 27, 2011·Nature Reviews. Cardiology·Norbert FreyHugo A Katus
Nov 8, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Christine SchrammMaike Krenz
Jan 27, 2012·Development·Yvette LangdonFrank L Conlon
Jul 31, 2012·Biochemistry Research International·Kerry S McDonaldCraig A Emter
Oct 31, 2012·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·Daniel L JacobyWilliam J McKenna
Oct 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mylène TajanArmelle Yart

❮ Previous
Next ❯

Citations

Jun 19, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Charmain A FernandoSteven S Segal
Dec 13, 2016·JCI Insight·Jae-Sung YiAnton M Bennett
Jun 23, 2019·Journal of Molecular and Cellular Cardiology·Alexey V DvornikovXiaolei Xu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Related Papers

American Journal of Physiology. Heart and Circulatory Physiology
Christine SchrammMaike Krenz
Current Hypertension Reports
Darrell D Belke, Wolfgang H Dillmann
Circulation Journal : Official Journal of the Japanese Circulation Society
Michihiko Tada
© 2022 Meta ULC. All rights reserved