Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC153
Ageing produces a distinct molecular fingerprint in the failing ovine ventricular myocardium
J. L. Caldwell1, M. A. Horn1, D. A. Eisner1, K. M. Dibb1, A. W. Trafford1
1. Unit of Cardiac Physiology, Manchester Academic Health Sciences Centre, Manchester, United Kingdom.
Heart failure is characterised by decreased contractile performance of the heart. Dibb et al (2004) have previously demonstrated, in an ovine model of ageing, differences in intracellular calcium homeostasis in the ventricle are similar to those in early heart disease (Mørk et al. 2007). The aim of the present work was to extend these observations and determine if heart failure in the aged results in different response of calcium homeostatic proteins to that in the young. Under isoflurane anaesthesia (2-4% in oxygen) sheep were instrumented with a pacemaker and pacing lead. Post-operative analgesia (meloxicam 0.5mg/kg) and antibiosis (enrofloxacin 2.5mg/kg) were provided for 24 hr. Heart failure was induced by rapid ventricular pacing (Briston et al,. 2011) for 4-5 weeks. Following pentobarbitone euthanasia (200 mg/kg iv) samples of left ventricular myocardium were snap frozen. Age-matched non-instrumented animals served as controls. Western blotting was performed using standard methods and protein immunoreactivity quantified by chemiluminescence. Table 1 summarises the percentage changes in expression for several candidate proteins known to influence intracellular calcium homeostasis. Ageing alone resulted in a decrease in the calcium buffer calsequestrin and increases in protein phosphatase 1 and 2a (P<0.05, Students t-test). Qualitative differences were observed in the protein expression profiles between young and aged failing hearts (relative to age-matched control tissue). Notably, in comparison to young failing hearts where no change in SERCA or the SERCA : phospholamban ratio or CAMKIIδ was observed, in aged-failing hearts these were decreased. Conversely, in young failing hearts protein phosphatase expression increases whereas in aged failing myocardium neither PP1 nor PP2a changed. In summary, there appears to be distinct calcium homeostatic protein expression profile differences between young and aged failing hearts. Whether these differences result in alterations to the properties of the Ca2+ transient remain to be determined.
Where applicable, experiments conform with Society ethical requirements