Restoration of calcium handling properties of adult cardiac myocytes from hypertrophied hearts.
Reductions in cardiac sarcoplasmic reticulum calcium-ATPase (Serca2a) levels are thought to underlie the prolonged calcium (Ca(2+)) transients and consequent reduced contractile performance seen in human cardiac hypertrophy and heart failure. In freshly isolated cardiac myocytes from rats with monocrotaline-induced right ventricular hypertrophy we found reduced sarcoplasmic reticulum Serca2a expression and prolonged Ca(2+)transients, characteristic of hypertrophic cardiac disease. Modulation of intracellular Ca(2+)levels, Ca(2+) kinetics or Ca(2+)sensitivity is the focus of many current therapeutic approaches to improve contractile performance in the hypertrophic or failing heart. However, the functional effects of increasing Serca2a expression on Ca(2+) handling properties in myocytes from an animal model of cardiac hypertrophy are largely unknown. Here, we describe enhancement of the deficient Ca(2+) handling properties evident in myocytes from hypertrophied hearts following adenoviral-mediated transfer of the human Serca2a gene to these myocytes. These results highlight the importance of Serca2a deficiencies in the hypertrophic phenotype of cardiac muscle and suggest a simple, effective approach for manipulation of normal cardiac function.
Reilly
A M
AM
Molecular Physiology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Australia.
Petrou
S
S
Panchal
R G
RG
Williams
D A
DA
D000257:Adenoviridae Infections / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006332:Cardiomegaly / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005822:Genetic Vectors / Q000138:chemical synthesis; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D016686:Monocrotaline / Q000008:administration & dosage; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D016686:Monocrotaline; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium