Sympathetic modulation of the cardiac myocyte phenotype: studies with a cell-culture model of myocardial hypertrophy.
Myocardial hypertrophy is the common endpoint of many cardiovascular stimuli such as hypertension, myocardial infarction, valvular disease, and congestive failure. Catecholamines have long been implicated in the pathogenesis of myocardial hypertrophy, however, it is very difficult to sort out catecholamine mechanisms in vivo. We have developed a cell-culture model which excludes hemodynamic effects and allows the assignment of receptor specificity to catecholamine effects. Utilizing this system, we have shown that stimulation of the alpha 1 adrenergic receptor leads to the development of myocardial hypertrophy and results in the selective up-regulation of the fetal/neonatal mRNAs encoding skeletal alpha-actin and beta-MHC, a pattern similar to that seen with hypertrophy in-vivo. Utilizing a co-transfection assay, we have also obtained data that suggest that the beta-PKC isozyme is in a pathway regulating transcription of the beta-MHC isogene. Beta adrenergic stimulation of the cultured cardiac myocytes also results in a modest degree of hypertrophy, however, this effect may be dependent upon myocyte contractile activity and may involve, at least in part, the non-muscle cells present in the culture system.
Long
C S
CS
Cardiology Section, Veterans Administration Medical Center, San Francisco, California.
Kariya
K
K
Karns
L
L
Simpson
P C
PC
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology* / Q000235:genetics; D002395:Catecholamines / Q000502:physiology; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D007536:Isomerism; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology*; D010641:Phenotype; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014158:Transcription, Genetic
D002395:Catecholamines; D003285:Contractile Proteins; D006133:Growth Substances; D011942:Receptors, Adrenergic, alpha