Role of PKCδ in Enhanced Expression of Gqα/PLCβ1 Proteins and VSMC Hypertrophy in Spontaneously Hypertensive Rats

Gq alpha signaling has been implicated in cardiac hypertrophy. In addition, angiotensin II (Ang II) was also shown to induce its hypertrophic effect through Gqa and PKC delta activation. We recently showed the role of enhanced expression of Gq alpha/PLC beta 1 proteins in vascular smooth muscle cell (VSMC) hypertrophy, however, the role of PKCd in VSMC hypertrophy in animal model is still lacking. The present study was therefore undertaken to examine the role of PKCd and the associated signaling mechanisms in VSMC hypertrophy using 16-week-old spontaneously hypertensive rats (SHR). VSMC from 16-week-old SHR exhibited enhanced phosphorylation of PKC delta-Tyr(311) and increased protein synthesis, marker of hypertrophy, as compared to WKY rats which was attenuated by rottlerin, an inhibitor of PKCd. In addition, knocking down of PKCd by PKC delta-siRNA also attenuated enhanced protein synthesis in VSMC from SHR. Furthermore, rottlerin attenuated the increased production of superoxide anion, NAD(P) H oxidase activity, increased expression of Gqa, phospholipase C(PLC)beta 1, insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor ( EGFR) proteins in VSMC from SHR. In addition, the enhanced phosphorylation of c-Src, PKC delta-Tyr(311), IGF-1R, EGFR and ERK1/2 exhibited by VSMC from SHR was also attenuated by rottlerin. These results suggest that VSMC from SHR exhibit enhanced activity of PKCd and that PKCd is the upstream molecule of reactive oxygen species (ROS) and contributes to the enhanced expression of Gqa and PLC beta 1 proteins and resultant VSMC hypertrophy involving c-Src, growth factor receptor transactivation and MAP kinase signaling.