Upregulation of phospholipase D in heart hypertrophy*

Objectives: Evidence for a major role of phospholipase D (PLD) in cellular proliferation and growth is accumulating. PLD produces phosphatidic acid which recruits proteins and regulates protein and lipid kinase activities. Does PLD play any role in cardiac hypertrophy?

Material and Methods: In rat heart, aortic banding caused a significant hypertrophy (as shown by tissue mass and ANP expression) in left ventricles after 50 days and in right ventricles after >100 days.

Results: The hypertrophy was accompanied by small increases of basal PLD activity and massive increases of PLD activities stimulated by phenylephrine and phorbol ester. In left hypertrophied ventricles, the expression of both PLD1 and PLD2 was enhanced as shown by RT-PCR and Western blot. PLD protein expression was also investigated in 4 hypertrophied and 4 normal left ventricles of patients (aged 17–65 years). In contrast to rat heart, PLD1 was more prominent than PLD2 in human tissue. In hypertrophied ventricles, both PLD isoforms were drastically up-regulated (relative to mass and protein of tissue).

Conclusions: Pressure overload-hypertrophy of left ventricles enhanced PLD1 and PLD2 expression in rat and human heart and potentiated PLD activation by a-adrenoceptors and protein kinase C stimulation in the experimental model. These results are compatible with a role of PLD activation in cardiac hypertrophy cell signalling.

*Supported by the Deutsche Forschungsgemeinschaft (Lo 196/11).