FIG. 7.

The inhibitory effect of cGMP on RhoA-mediated protein synthesis and SRE-dependent gene transcription is reversed by the smooth muscle-targeted expression of RhoA^A188. (A and B) MASMCs were derived from NTg, RhoA^WT-Tg, and RhoA^A188-Tg mice. (A) Effects of 8-Br cGMP and Y-27632 on Ang II-induced protein synthesis, as assessed by [³H]leucine uptake (left), and on serum-induced DNA synthesis, as assessed by [³H]thymidine uptake (right). Values are means ± SEM for six replicates. #, P < 0.0001; †, P < 0.05 versus serum-starved NTg cells; §, P < 0.0001 versus Ang II-treated NTg cells; ¶, P < 0.0001 versus Ang II- and Y-27632-treated RhoA^A188-Tg cells; NS, not significant. (B) Effects of 8-Br cGMP and Y-27632 on TGF-β-induced SRE (left)- and AP-1 (right)-dependent transcriptional activity. Values are means ± SEM for triplicates. #, P < 0.0001; †, P < 0.05 versus serum-starved NTg cells; §, P < 0.0001 versus TGF-β-treated NTg cells; ¶, P < 0.0001 versus TGF-β- and Y-27632-treated RhoA^A188-Tg cells. (C) Proposed model showing in vivo pathways whereby pro- and antifibrotic signals converge intracellularly. (D) cGK I is a major determinant of RhoA activity and controls the relative contributions of RhoA to the cellular profibrotic pathways in normal (left) and cGK I-deficient (right) blood vessels.