PKC and TGF-β1 expressions in pulmonary artery of pulmonary hypertension rats and regulation of 5-HT2A receptor antagonist on them

Objective: To explore the possible mechanisms of 5-HT2A receptor involved in the proliferation of pulmonary artery smooth muscle cells. Methods: Pulmonary hypertension rat models were established by intraperitoneal injection of monocrotaline. Rats in the treatment group were treated with 5-HT2A receptor antagonists (sarpogrelate hydrochloride) for three weeks while those in the control group were intraperitoneally given sodium chloride. The morphological changes of peripheral pulmonary artery were observed with hematoxylin and eosin staining method; the expressions of TGF-β1 and PKC in the pulmonary artery were detected by Western blotting and RT-PCR. Results: Compared with the control group, mPAP and RV/(LV+S)% were increased significantly in the model group (both P<0.05). The endothelial cells shedded or disappeared, the pulmonary artery wall thickened, and the lumen narrowed. In the model group, the protein and mRNA expressions of TGF-β1 and PKC were increased. Compared with the model group, mPAP and RV/(LV+S)% decreased markedly in the treatment group (P<0.05; P<0.01). The media thickness and stenosis in the treatment group were significantly improved. In the treatment group, the protein and mRNA expressions of TGFβ1 and PKC were decreased (P<0.05; P<0.01). Conclusion: 5-HT2A receptor antagonists can reduce pulmonary artery pressure and improve the pulmonary arterial remodeling induced by pulmonary arterial hypertension through PKC/TGF-β1 signal pathway.