January 1, 1991Open Access
Mechanisms of Cardiac Hypertrophy and Injury. Possible Role of Protein Kinase C Activation.
Key Result
Mechanical stretching of rat cardiocytes and in vivo pressure overload increased c-fos and TGF-beta expression, suggesting hemodynamic overload induces hypertrophy via protein kinase C activation.
Structured PICO
P
Population
Cultured rat neonatal cardiocytes, in vivo heart models of pressure overload, and cultured cardiac fibroblasts
I
Intervention
In vitro mechanical load by stretching adherent cells and in vivo pressure overload
O
Outcome
Total cell RNA content, mRNA levels of c-fos, inositol phosphate levels, TGF beta expression, and collagen synthesissurrogate
Hemodynamic overload may stimulate cardiac hypertrophy and induce cardiac fibrosis through protein kinase C activation.
Abstract
To examine the molecular mechanisms by which mechanical stimuli induced cardiac hypertrophy and injury, we cultured rat neonatal cardiocytes in deformable dishes and imposed an in vitro mechanical load by stretching the adherent cells. Myocyte stretching increased total cell RNA content and mRNA levels of c-fos. Marked accumulation of c-fos mRNA followed increases in intracellular Na+ and protein kinase C activation. The accumulation of c-fos mRNA by cardiocyte stretching was suppressed by protein kinase C inhibitors but not by stretch channel blockers. Moreover, myocyte stretching increased inositol phosphate levels, and activation of protein kinase C by phorbolesters stumulated the expression of c-fos. We also examined TGF beta expression in the heart. TGF beta is known to be stimulated by protein kinase C activation, and the mRNA level of TGF beta was increased in in vivo heart by pressure overload. Furthermore, collagen synthesis was stimulated by TGF beta in cultured fibroblasts from hearts. These findings suggest that hemodynamic overload may stimulate cardiac hypertrophy and induce cardiac injury (fibrosis) through protein kinase C activation.