Cardiac contractile proteins in hypertrophied and failing Guinea pig heart

Ashwani Malhotra, Francis M. Siri, Ronald Aronson

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

Abstract

Objective: The aim was to study changes in contractile proteins which accompany marked hypertrophy and heart failure in mammalian hearts initially containing predominantly V3 isomyosin. Methods: Left ventricular myosin and myofibrillar ATPase activity and right ventricular actomyosin ATPase activity were measured in normal Guinea pig hearts, in hearts which were hypertrophied as a result of progressive left ventricular systolic overload following ascending aortic banding, and in hypertrophied hearts from animals which showed signs of overt congestive heart failure. Male Guinea pigs weighing 225-275 g at the time of aortic banding were used for the studies. Results: Left ventricular myosin and myofibrillar ATPase activity and right ventricular actomyosin ATPase activity were correlated with body weight, left and right ventricular weight, and left ventricular peak systolic pressure during aortic occlusion. Left ventricular myosin ATPase activity and right ventricular actomyosin ATPase activity were markedly depressed in hypertrophied ventricles compared to control ventricles. Cardiac myofibrillar ATPase activity was lower in hypertrophied failing hearts than in control hearts over a wide range of calcium concentrations. In control animals and in those without heart failure, there was a nearly identical inverse relationship between left ventricular mass up to 1600 mg and myosin ATPase activity. Hypertrophied failing hearts were larger but showed little further reduction in cardiac myosin ATPase activity. Representative gel scans of non-dissociating pyrophosphate gels of left ventricular myosin from an 8 d postoperative aortic constricted animal and from its age and weight matched control showed predominantly Vi isomyosin with small amounts of Vi isoenzyme. However, preparations taken from Guinea pigs 16 d after aortic constriction showed only the Vi isoform, whereas the Vi isoform was still apparent in control. Hypertrophied failing left ventricles developed less pressure per unit mass during brief aortic occlusion than non-failing left ventricles with comparable myosin ATPase activities. Conclusions: These observations raise important questions as to the distribution of myosin isoforms in the normal adult Guinea pig, and the possibility that myosin ATPase activity might be altered by post-translational modification. Although cardiac myosin ATPase activity correlates with left ventricular performance, it cannot fully explain the depressed performance of failing hearts in this model. Additional immunological studies of cardiac contractile proteins are required as well as studies designed to explore the implications of altered myosin ATPase activity for both contractile function and overall cellular homeostasis.

Original languageEnglish
Pages (from-to)153-161
Number of pages9
JournalCardiovascular Research
Volume26
Issue number2
DOIs
StatePublished - Feb 1992
Externally publishedYes

Keywords

  • Cardiac hypertrophy
  • Isoenzyme
  • Myofibrils
  • Myosin

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