Abstract
Hemodynamic load is a major determinant of cardiac mass and its phenotype, but very little is known about how mechanical load is converted into intracellular signals of gene expression and regulation. We have shown earlier that factors other than blood pressure control play a role in the mechanism involved in the development or regression of myocardial hypertrophy. We have identified a soluble factor, myotrophin, from the hearts of spontaneously hypertensive rats and dilated cardiomyopathic humans, which stimulates protein synthesis both in neonatal and adult rat cardiac myocytes. Myotrophin gene has been mapped and shown to be a novel gene localized in human chromosome 7q-33. The present study was conducted to evaluate the mechanism by which myotrophin is released and in turn initiates myocardial hypertrophy. We used an in vitro model, where neonatal cardiac myocytes were grown on stretchable plates and examined the effect of stretch on myotrophin gene expression (to mimic pressure overload), an in vivo model using beating non-working hearts exposed to high pressure and three different models of hypertensive rats. Our data showed that both cyclic stretch and exposure to high pressure caused significant increase in the transcript levels of myotrophin followed by expression of β-myosin heavy chain and atrial natriuretic factor associated with an increase in myocardial protein synthesis. All three models of hypertensive rats also showed a significant increase in myotrophin transcripts. Altogether, our data strongly suggest that stretching of the cells by pressure or volume turns on the myotrophin, which in turn is responsible for the initiation process of myocardial hypertrophy in response to pressure or volume overload. (Mol Cell Biochem 262: 79–89, 2004)
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Sil, P., Gupta, S., Young, D. et al. Regulation of myotrophin gene by pressure overload and stretch. Mol Cell Biochem 262, 79–89 (2004). https://doi.org/10.1023/B:MCBI.0000038219.46896.a4
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DOI: https://doi.org/10.1023/B:MCBI.0000038219.46896.a4