Cardiac response to pressure overload in the rat: the selective alteration of in vitro directed RNA translation products.

Abstract

As cardiac hypertrophy develops, total cardiac RNA and protein synthesis increase significantly. We have identified specific messenger RNAs that change in predominance with the induction of pressure-overload-stimulated cardiac hypertrophy. Total cardiac RNA was isolated from rats either undergoing cardiac hypertrophy secondary to subdiaphragmatic aortic constriction or subjected to sham surgery. The products translated in vitro were separated by two-dimensional gel electrophoresis and quantitated. The translation of four proteins decreased while the translation of four others increased in preparations from hypertrophied hearts compared with those from sham-treated rats. Two isoforms of creatine kinase M were translated in vitro. Only one of these isoforms decreased with cardiac hypertrophy, suggesting that the transcriptional or translational control for creatine kinase is much more complex than previously believed. Finally, since only eight of over 700 different translation products changed in relative predominance with cardiac hypertrophy, we conclude that the accumulation of existing RNA and protein products is the primary adaptive process responsible for cardiac hypertrophy.

RNA transcription and translation in the hearts of normal and cardiomyopathic Syrian hamsters

“…This observation is similar to Ouellette et al (1987) who detected a decrease in only three minor protein products, which appeared to be dependent upon the progression of the cardiomyopathic disease process (i.e., the age of the diseased animals). Similar results have also been reported by Boheler and Dillmann (1988) using myocardial pressure overload in rats. Although these observations indicate that there are altered transcriptional products in the myocardium of the myopathic hamster, they do not imply that these changes are the primary cause of cardiomyopathy.…”

“…In the myocardium, any or all of these regulatory processes may be altered during the course of myocardial growth or during the evolution of diseases such as cardiomyopathy (Liew and Sole 1978a, 19786;Jackowski and Liew 1983;Malhotra et al 1985;Ouellette et al 1987;Boheler and Dillmann 1988). Our results indicate that cardiac RNA transcription decreases 10-fold from 7 to 210 days of age in both normal and cardiomyopathic Syrian hamsters.…”

“…Although these observations indicate that there are altered transcriptional products in the myocardium of the myopathic hamster, they do not imply that these changes are the primary cause of cardiomyopathy. Boheler and Dillmann (1988) reported that only eight protein products were altered in comparison to those of matched sham-operated myocardium with four protein products being elevated and four decreased. Since only eight of the over 700 protein products showed any change, the authors speculated that there was an amplification of existing mechanisms for RNA and protein accumulation (Boheler and Dillmann 1988).…”

“…Boheler and Dillmann (1988) reported that only eight protein products were altered in comparison to those of matched sham-operated myocardium with four protein products being elevated and four decreased. Since only eight of the over 700 protein products showed any change, the authors speculated that there was an amplification of existing mechanisms for RNA and protein accumulation (Boheler and Dillmann 1988). Our results confirm this hypothesis and indicate that even though there is a coordinate decrease in RNA transcriptional and translational mechanisms, alterations in protein product synthesis in a controlled in vitro environment is not affected.…”

Rapid gene transcription induced by stretch in cardiac myocytes and fibroblasts and their paracrine influence on stationary myocytes and fibroblasts

“…In a quantitative sense, there is an overall increase in cardiac expression of constitutively expressed genes, leading ultimately to myocyte hypertrophy. Myocardial contents of total ribonucleic acid (RNA), messenger RNA (mRNA) and transfer RNA (tRNA) expressed per unit tissue mass are increased during the hypertrophic process [2,23,24,25]. The qualitative changes in gene expression include positive and negative modulation of cardiac-specific genes and a shift in the expression of several isogenes towards a fetal gene repertoire [12,15,34].…”