Alterations in protein kinase C isoenzyme expression and autophosphorylation during the progression of pressure overload-induced left ventricular hypertrophy

Cardiomyocytes express several isoenzymes of protein kinase C (PKC), which as a group have been implicated in the induction of left ventricular hypertrophy (LVH) and its transition to heart failure. Individual PKC isoenzymes also require transphosphorylation and autophosphorylation for enzymatic activity. To determine whether PKC isoenzyme expression and autophosphorylation are altered during LVH progression in vivo, suprarenal abdominal aortic coarctation was performed in Sprague-Dawley rats. Quantitative Western blotting was performed on LV tissue 1, 8 and 24 weeks after aortic banding, using antibodies specific for total PKCα, PKCδ and PKCε, and their C-terminal autophosphorylation sites. Aortic banding produced sustained hypertension and gradually developing LVH that progressed to diastolic heart failure over time. PKCε levels and autophosphorylation were not significantly different from sham-operated controls during any stage of LVH progression. PKCα expression levels were also unaffected during the induction of LVH, but increased 3.2 ± 0.8 fold during the transition to heart failure. In addition, there was a high degree of correlation between PKCα levels and the degree of LVH in 24 week banded animals. However, autophosphorylated PKCα was not increased at any time point. In contrast, PKCδ autophosphorylation was increased prior to the development of LVH, and also during the transition to heart failure. The increased PKCδ autophosphorylation in 1 week banded rats was not accompanied by an increase in total PKCδ, whereas total PKCδ levels were markedly increased (6.0 ± 1.7 fold) in 24 week banded animals. Furthermore, both phosphorylated and total PKCδ levels were highly correlated with the degree of LVH in 24 week banded rats. In summary, we provide indirect evidence to indicate that PKCδ may be involved in the induction of pressure overload LVH, whereas both PKCδ and PKCα may be involved in the transition to heart failure.