Responses of PKCε to cardiac overloads on myocardial sympathetic innervation and NET expression.

Abstract

Protein kinase C (PKC) is a key mediator of many diverse physiological and pathological responses. PKC activation play an important regulatory role of cardiac function. The present study was performed to investigate whether there were differential activations of the PKCε and how the activation coupled with norepinephrine transporter (NET) surface expression, sympathetic innervation pattern and extracellular matrix remodeling in different cardiac hemodynamic overloads induced by abdominal aortic constriction or aortocaval fistula. At 8weeks after the operations, heart failure were induced, accompanied with myocardial hypertrophy, which was more pronounced in pressure overload (POL) than that of volume overload (VOL) rats, left ventricular dysfunction and increased plasma norepinephrine (NE). In POL rats there was an increase in myocardial collagen deposition, in contrast, the amount decreased in VOL as compared with the sham rats. POL remarkably upregulated PKCε membrane-cytosol ratio and downregulated NET membrane fraction, whereas, in VOL induced opposite changes. Accompanied with the PKCε activation, nerve sprouting, evidenced by myocardial GAP43 protein increased, and different nerve phenotypes were found, in POL tyrosine hydroxylase (TH) positive nerve density increased with NET and choline acetyltransferase (ChAT) immunoreactivity density decreased, in contrast, in VOL NET and ChAT increased, TH did not change. The overloads did not induce alteration of NET mRNA expression, but resulted in different myocardial β1-AR mRNA expression, in POL β1-AR mRNAwas significantly downregulated, while in VOL rats unaltered. Conclusion, the present results suggested that the different cardiac hemodynamic overload could differentially activate a common signaling, PKCε intermediate and thereby generate biological diversity.