OBJECTIVE To observe the effects of rosiglitazone on signaling pathway of angiotensin Ⅱ (Ang Ⅱ)-induced C-reactive protein (CRP) expression in human aortic endothelial cells (HAECs).METHODS HAECs were pretreated with the different concentrations of rosiglitazone 18 h before stimulation with Ang Ⅱ for 12 h.Then, mRNA of CRP and AT1 was analyzed by RT-PCR, and the protein expressions of CRP, AT1, p-JNK, p-ERK1/2, JNK and ERK1/2 in HAECs were analyzed by western blot respectively.HAECs were pretreated with losartan, PD123319 for 1 h or rosiglitazone for 18 h prior to stimulation with Ang Ⅱ for 12 h.Then,the cells were incubated for 1 h with H2DCF-DA.Finally, the fluorescent intensity was measured by a fluorescence microscope.RESULTS Pretreatment of the cells with rosightazone for 18 h obviously reduced Ang Ⅱ-induced mRNA and protein expressions of CRP and AT1.Losartan and rosiglitazone obviously inhibited Ang Ⅱ-stimulated ROS generation, while PD123319 showed no significantly inhibitory effect on ROS production in HAECs.Preincubation of the cells with rosiglitazone for 18 h obviously downregnlated Ang Ⅱ-caused phosphorylation of ERK1/2 and JNK in HAECs.Thus, rosiglitazone is able to inhibit Ang Ⅱ-induced CRP expression in HAECs, and probably through interfering with AT1-ROS-MAPK signal pathway.DISCUSSION As an inflammatory molecule, CRP plays a direct role in atherogenesis.Our previous study confirmed that Ang Ⅱ is capable of inducing CRP generation in HAECs, which is through AT1-ROS-ERK1/2 and JNK-NF-κB signaling pathway.In the present study, we observed that rosiglitazone attenuated Ang Ⅱ-induced CRP expression in HAECs, which implies that rosiglitazone may counteract vascular inflammation and thus exerts a beneficial effect in prevention of atherosclerosis.It is well known that most of the deleterious effects of Ang Ⅱ are accomplished through AT1 receptor.The present results showed that Ang Ⅱ upregulates AT1 expression, whereas rosiglitazone reduced Ang Ⅱ-induced AT1 expression in HAECs.As AT1 receptor mediates Ang Ⅱ-induced CRP expression in HAECs, it is suggested that the inhibitory effect of rosiglitazone on Ang Ⅱ-induced CRP production is related to inhibiting AT1 expression in HAECs.We found that rosiglitazone and AT1 blocker losartan both decreased Ang Ⅱ-stimulated ROS production in HAECs.Since AT1 receptor mediates ROS generation and ROS participate in the regulation of Ang Ⅱ-induced CRP expression in HAECs, rosiglitazone reduces CRP production in HAECs possibly via interfeting with AT1 expression and subsequent ROS generation.ERK1/2 and JNK activation is associated with Ang Ⅱ-induced CRP production in HAECs.In the present study, we observed that rosiglitazone restrained Ang Ⅱ-induced phosphorylation of ERK1/2 and JNK, suggesting that ERK1/2 and JNK inactivation also contributes to inhibition by rosiglitazone of Ang Ⅱ-induced CRP production.In summary, the present study demonstrates that rosiglitazone is able to inhibit Ang Ⅱ-induced CRP generation in HAECs.The mechanisms responsible for the effect of rosightazone involve AT1 downregulation, subsequent ROS decrease and ERK1/2, JNK inactivation.These results strengthen understanding of anti-inflammatory and anti-atherosclerotic effects of rosiglitazone.