Imperial College London

ProfessorSteveMarston

Faculty of MedicineNational Heart & Lung Institute

(Non-Clinical) Professor in Cardiovascular Biochemistry
 
 
 
//

Contact

 

+44 (0)20 7594 2732s.marston Website

 
 
//

Location

 

433ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Toepfer:2016:10.1152/ajpheart.00899.2015,
author = {Toepfer, CN and Sikkel, MB and Caorsi, V and Vydyanath, A and Torre, I and Copeland, O and Lyon, AR and Marston, SB and Luther, PK and MacLeod, KT and West, TG and Ferenczi, MA},
doi = {10.1152/ajpheart.00899.2015},
journal = {American Journal of Physiology - Heart and Circulatory Physiology},
pages = {H465--H475},
title = {A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation.},
url = {http://dx.doi.org/10.1152/ajpheart.00899.2015},
volume = {311},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Myocardial remodeling in response to chronic myocardial infarction (CMI) progresses through two phases, hypertrophic 'compensation' and congestive 'decompensation'. Nothing is known about the ability of un-infarcted myocardium to produce force, velocity, and power during these clinical phases, even though adaptation in these regions likely drive progression of compensation. We hypothesized that enhanced crossbridge-level contractility underlies mechanical compensation and is controlled in part by changes in the phosphorylation states of myosin regulatory proteins. We induced CMI in rats by left anterior descending coronary artery ligation. We then measured mechanical performance in permeabilized ventricular trabecula taken distant from the infarct zone and assayed myosin regulatory protein phosphorylation in each individual trabecula. During full activation, the compensated myocardium produced twice as much power and 31% greater isometric force compared to non-infarcted controls. Isometric force during submaximal activations was raised >2.4-fold, whilst power was 2-fold greater. EM and confocal microscopy demonstrated that these mechanical changes were not a result of increased density of contractile protein, and therefore not an effect of tissue hypertrophy. Hence, sarcomere-level contractile adaptations are key determinants of enhanced trabecular mechanics and of the overall cardiac compensatory response. Phosphorylation of myosin regulatory light chain (RLC) increased and remained elevated post-MI, while phosphorylation of myosin binding protein-C (MyBP-C) was initially depressed but then increased as the hearts became decompensated. These sensitivities to CMI are in accordance with phosphorylation-dependent regulatory roles for RLC and MyBP-C in crossbridge function and with compensatory adaptation in force and power that we observed in post-CMI trabeculae.
AU - Toepfer,CN
AU - Sikkel,MB
AU - Caorsi,V
AU - Vydyanath,A
AU - Torre,I
AU - Copeland,O
AU - Lyon,AR
AU - Marston,SB
AU - Luther,PK
AU - MacLeod,KT
AU - West,TG
AU - Ferenczi,MA
DO - 10.1152/ajpheart.00899.2015
EP - 475
PY - 2016///
SN - 0363-6135
SP - 465
TI - A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation.
T2 - American Journal of Physiology - Heart and Circulatory Physiology
UR - http://dx.doi.org/10.1152/ajpheart.00899.2015
UR - http://hdl.handle.net/10044/1/34272
VL - 311
ER -