DESMIN GENE-EXPRESSION IN CARDIAC MYOCYTES IS RESPONSIVE TO CONTRACTILE ACTIVITY AND STRETCH

Experiments were performed to assess the ability of mechanical stimuli , experienced by ventricular cardiac myocytes during the progression o f hypertrophic and dilated pathology, to increase the expression of de smin in cultured neonatal rat cardiac myocytes. Results indicate that both contractile activity and load due to passive stretch increase des min content in neonatal rat cardiac myocytes through increased desmin gene transcription. Western blot analysis demonstrated that contractio n induced a selective increase in desmin protein content in neonatal r at cardiac myocytes above increases observed in the content of total c ellular protein. Northern blot analysis indicated that desmin mRNA con tent increased in response to contraction as well as to alpha-adrenerg ic stimulation. Desmin mRNA content also increased in cultured neonata l myocytes in response to stretch. Angiotensin II (ANG II) treatment o f contracting neonatal cardiac myocytes further increased desmin mRNA content, whereas similar treatment in arrested neonatal cardiac myocyt es failed to increase desmin mRNA. This contraction-dependent responsi veness to ANG II is not a function of increases in the density or rela tive subtype composition of ANG II receptors. Treatment of contracting neonatal rat cardiac myocytes with actinomycin D prevented increases in desmin mRNA content, suggesting regulation of transcription of the desmin gene by contraction. Nuclear run-on experiments indicate that c ontraction increases transcription of the desmin gene in cardiac myocy tes. These results are consistent with the modulation of desmin gene e xpression secondarily to changes in the mechanical environment that oc cur in cardiac tissue undergoing dilation or hypertrophy.