AIM: To investigate the effects of simvastatin on cigarette smoke extract(CSE)-induced expression levels of soluble endothelial cell protein C receptor(sEPCR) and membrane-associated endothelial cell protein C receptor(mEPCR) in human umbilical vein endothelial cells(HUVECs).METHODS: Cultured HUVECs at passage 4 to 6 were randomly divided into control group,5% CSE group,simvastatin groups and simvastatin+CSE groups.In simvastatin groups,HUVECs were incubated with simvastatin at the concentrations of 50,100 and 200 μmol/L for 24 h.In simvastatin+CSE groups,the cells were treated with simvastatin at the concentrations of 50,100 and 200 μmol/L for 2 h,and then exposed to CSE for 24 h.The protein level of sEPCR in the culture supernatants was measured by ELISA.The cells were collected for determining the mRNA expression of mEPCR by real-time PCR.RESULTS: Compared with control group,the protein level of sEPCR was significantly increased,and the mRNA expression of mEPCR was significantly decreased in 5% CSE group(both P0.05).The protein levels of sEPCR were significantly increased,and the mRNA expression of mEPCR was significantly decreased in 100 μmol/L and 200 μmol/L simvastatin groups.However,the protein levels of sEPCR were lower,and the mRNA expression of mEPCR was significantly higher in 100 μmol/L and 200 μmol/L simvastatin groups than those in 5% CSE group.Compared with 5% CSE group,the protein levels of sEPCR in simvastatin+CSE groups were significantly decreased,but higher than those in control group and simvastatin group with corresponding concentration.On the contrary,the mRNA expression of mEPCR in simvastatin+CSE groups was significantly increased,but lower than that in control group and simvastatin group with corresponding concentration(all P0.05).CONCLUSION: Simvastatin obviously increases the mRNA expression of mEPCR,decreases the protein level of sEPCR,and attenuates the CSE-induced endothelial injury in vitro.

Objective To investigate the expression variation of peroxisome proliferator-activated receptor γ (PPAR-γ) in pulmonary vasculature in rats exposed to cigarette smoke and its role in pulmonary vascular remodeling.Methods 30 male SD rats were randomly divided into a control group,a smoke exposure for 6 weeks group,a smoke exposure for 12 weeks group,with 10 rats in each group.The ratio of pulmonary vascular wall thickness/vascular external diameter (WT％)and the ratio of pulmonary vascular wall area/total pulmonary vascular area (WA％)were measured by the image analysis system.The expression of PPAR-γ protein in pulmonary vascular of each group was detected by Immunohistochemistry.Results ①WT％ and WA％ increased significantly in the smoke exposure for 6 weeks group [(45.61 ± 2.43)％,(59.69±12.59)％] and smoke exposure for 12 weeks group [(54.23 ±6.22) ％,(76.26±8.36)％] compared to those of control group [(32.89±7.65)％,(33.05±14.84)％] (all P＜0.05). The WT％ and WA％ in the smoke exposure for 12 weeks group increased significantly compared to those of smoke exposure for 6 weeks group (all P ＜0.05).②The expression of PPAR-γ protein in pulmonary vascular decreased significantly in the smoke exposure for 6 weeks group (0.48±0.08)and the smoke exposure for 12 weeks group (0.37±0.07) compared to control group (0.51±0.07)(all P＜0.05).The expression of PPAR-γ protein decreased in the smoke exposure for 12 weeks group compared to the smoke exposure for 6 weeks group (P＜0.05).③The expression of PPAR-γ protein in pulmonary vascular was respectively negatively correlated with WT％ and WA％ ( r =-0.715 and -0.683)(all P＜ 0.05).Conclusions By down-regulating the expression of PPAR-γ protein in pulmonary vascular,cigarette smoke exposure induces the remodeling of pulmonary vascular.

Objective To explore the effects of cigarette smoke exposure on pulmonary artery pressure and levels of endothelium nitric oxide synthase (eNOS) and nitric oxide (NO) of pulmonary vascular in rats.Methods Twenty-one male SD rats were divided randomly into control group (C group),smoke exposure one month group (S1m group) and smoke exposure three months group (S3m group),seven rats in each group.Mean right ventricular systolic pressure (mRVSP) and right ventricular hypertrophy index (RVHI) were observed.Nitrate reductase enzymatic was employed to detect the expression of NO in lung tissue.The expression of eNOS protein in pulmonary vascular was measured by immunohistochemistry.Results ① The mRVSP and RVHI in S3m group [(65.63 ± 0.93) mmHg,( 54.79 ± 7.13) ％]were significantly higher than those in S1 m group [ ( 23.57 ± 14.51 ) mm Hg,(36.62 ±1.32)％]and C group [(16.85±1.26) mmHg,(32.41±0.26)％](all P＜0.01).There were no statistical difference in mRVSP and RVHI between C group and S1m group ( P ＞0.05).②The eNOS protein expression of pulmonary vascular in SIm group and S3m group (0.32 ±0.04,0.24 ±0.03) were lower than that in group C (0.43 ± 0.06) (all P ＜0.01),and that in S3m group was lower than that in S1m group ( P ＜0.01).③The NO expression of lung tissue in S1m group and S3m group[ (1.98±0.20) μmol/gprot,(0.95± 0.09) μmol/gprot]was lower than that in group C [(2.98±0.19) μmol/gprot](all P ＜ 0.01 ),and that in S3m group was less than that in S1m group ( P ＜ 0.01 ).④ mRVSP was positively correlated with RVHI (r =0.713,P ＜0.01).NO in lung tissue was negatively correlated with mRVSP ( r=-0.615,P＜0.05).eNOS in pulmonary vascular was positively associated with NO in lung tissue ( r =0.944,P ＜ 0.01).Conclusions By down-regulating the expression of eNOS protein in endothelial cell of pulmonary vascular,cigarette smoke exposure induces the biosynthesis of NO,which induces the increase of pulmonary artery pressure,and the effect is time dependence in certain scope.