ENHANCED SERCA2 EXPRESSION AND PHOSPHOLAMBAN PHOSPHORILATED AT THR17 COULD BE ADAPTATIVE RESPONSE TO VENTRICULAR HYPERTHOPHY INDUCED BY PRESSURE OVERLOAD

In order to investigate the effects of cardiac hypertrophy on SERCA2 and PLB expression, two proteins implicated as important determinants in the deteriorated function of the failing heart, this study was undertaken in a rat model of pressure-overload induced hypertrophy. Left ventricular hypertrophy was induced by inserting a titanium haemoclip on the transverse section of aorta between the two common carotids in anaesthetized male Wistar rats (TAC group). At 14, 28, 42 or 56 days after surgery animals were sacrificed, the heart was removed and the left ventricle was separated, weighted and homogenated for Western blotting analysis. As control group we used animals that will undergo to surgery but not to stenosis (SHAM group). SERCA2 expression was significantly (P<0.005) higher in the left ventricles of TAC rats at any experimental times. Despite no significant differences in PLB expression between the two groups were observed, SERCA2/PLB ratio, calculated as an index of cardiac contractility, in TAC rats at 56 days was significantly (P<0.05) higher than SHAM rats. At 42 and 56 days the expression of PLB phosphorylated at Thr17 was significantly (P<0.05) higher in TAC rats compared to SHAM and we can observed a trend to increase in CaMkII expression, the protein kinase which phosphorylate PLB at Thr17, in TAC group. In conclusion our data let us to hypothesize that the enhanced expression of SERCA2 and subsequently the increased phosphorylation of PLB by CaMkII could be adaptative reactions to reduce an excess of free [Ca2+]I due to the pressure overload.