Objective. To study the effect of interleukin 10 (IL- 10) on the angiotensin II (AngII) stimulated rat VSMC proliferation and collagen secretion, and furthermore, explore its mechanism. Methods. On cultured VSMC of ra...Objective. To study the effect of interleukin 10 (IL- 10) on the angiotensin II (AngII) stimulated rat VSMC proliferation and collagen secretion, and furthermore, explore its mechanism. Methods. On cultured VSMC of rat, 3H- thymine (3H- TdR) and 3H- proline incorporations were used to evaluate the DNA and collagen synthesis, respectively. Western blot and immunoprecipitation were applied to assay the expression and activity of focal adhesion kinase (FAK), respectively. Results. IL- 10 (10－ 8～ 10－ 10g/ml) inhibited the increase of 3H- TdR and 3H- proline incorporation as well as FAK activity, which was induced by 10－ 7mol/L AngII (P< 0.05 or P< 0.01). IL- 10 also obviously downregulated the synthesis and secretion of collagen by AngII stimulated VSMC. But there was no difference in the protein expression of FAK among all the groups (P >0.05). Conclusion. IL- 10 antagonizes the VSMC proliferation and collagen synthesis by regulating FAK activity stimulated by AngII.展开更多
The present study investigated the role of calcineurin in angiotensin II(AngII)- induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calci...The present study investigated the role of calcineurin in angiotensin II(AngII)- induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII- treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H- leucine incorporation; atrial natriuretic factor(ANF) mRNA level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13％ ,57％ (P Conclusion. During AngII- induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII- induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII- induced myocardial hypertrophy of rats.展开更多
Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6...Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit＋ bosentan group and Nit＋ losartan group. Nitroglycerin tolerance was induced by 2- day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg－ 1· d－ 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg－ 1· d－ 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit＋ losartan group and Nit＋ bosentan group compared with Nit group [(31.95± 4.45 )％ vs (21.00± 3.69 )％ , P< 0.01 and (33.18± 6.16 )％ vs (21.00± 3.69 )％ , P< 0.01 ,respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50％ of the maximal response to SNP) was found in tolerant group[(34± 10) nmol/ L,P < 0.01 .The ET- 1 amounts in plasma and vascular tissue were markedly increased by 54％ and 60％ in Nit group compared with those in control group(P< 0.01).The ET- 1 amounts in plasma and vascular tissue were decreased by 30％ and 37％ in Nit＋ losartan group compared with those in Nit group (P< 0.01). Conclusion. Endothelin receptor antagonist and angiotensinⅡ receptor antagonist could prevent against the Nit tolerance .展开更多
Objective To evaluate the effect of angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)therapy on the prognosis of patients with atrial fibrillation(AF).Methods A total of 1,991 AF patie...Objective To evaluate the effect of angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)therapy on the prognosis of patients with atrial fibrillation(AF).Methods A total of 1,991 AF patients from the AF registry were divided into two groups according to whether they were treated with ACEI/ARB at recruitment.Baseline characteristics were carefully collected and analyzed.Logistic regression was utilized to identify the predictors of ACEI/ARB therapy.The primary endpoint was all-cause mortality,while the secondary endpoints included cardiovascular mortality,stroke and major adverse events(MAEs)during the one-year follow-up period.Univariable and multivariable Cox regression were performed to identify the association between ACEI/ARB therapy and the one-year outcomes.Results In total,759 AF patients(38.1%)were treated with ACEI/ARB.Compared with AF patients without ACEI/ARB therapy,patients treated with ACEI/ARB tended to be older and had a higher rate of permanent AF,hypertension,diabetes mellitus,heart failure(HF),left ventricular ejection fraction(LVEF)<40%,coronary artery disease(CAD),prior myocardial infarction(MI),left ventricular hypertrophy,tobacco use and concomitant medications(all P<0.05).Hypertension,HF,LVEF<40%,CAD,prior MI and tobacco use were determined to be predictors of ACEI/ARB treatment.Multivariable analysis showed that ACEI/ARB therapy was associated with a significantly lower risk of one-year all-cause mortality[hazard ratio(HR)(95%CI):0.682(0.527-0.882),P=0.003],cardiovascular mortality[HR(95%CI):0.713(0.514-0.988),P=0.042]and MAEs[HR(95%CI):0.698(0.568-0.859),P=0.001].The association between ACEI/ARB therapy and reduced mortality was consistent in the subgroup analysis.Conclusions In patients with AF,ACEI/ARB was related to significantly reduced one-year all-cause mortality,cardiovascular mortality and MAEs despite the high burden of cardiovascular comorbidities.展开更多
目的探讨ABI家族成员3结合蛋白(ABI family member 3-binding protein,ABI3BP)在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导内皮祖细胞功能障碍中的作用及机制。方法为探讨ABI3BP在AngⅡ诱导内皮祖细胞功能障碍中的作用,将细胞分为4组,sh-N...目的探讨ABI家族成员3结合蛋白(ABI family member 3-binding protein,ABI3BP)在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导内皮祖细胞功能障碍中的作用及机制。方法为探讨ABI3BP在AngⅡ诱导内皮祖细胞功能障碍中的作用,将细胞分为4组,sh-NC组[转染阴性对照短发夹RNA(LV-scramble-shRNA)+磷酸盐缓冲液(phosphate buffered saline,PBS)]、sh-ABI3BP组[转染ABI3BP shRNA(LV-ABI3BP-shRNA)+PBS]、sh-NC+AngⅡ组(LV-scramble-shRNA+AngⅡ)和sh-ABI3BP+AngⅡ组(LV-ABI3BP-shRNA+AngⅡ)。采用Transwell实验检测细胞迁移能力,黏附实验检测细胞黏附能力,Matrigel检测细胞成管能力,原位末端标记法检测细胞凋亡。Western blot检测整合素β1-黏着斑激酶(focal adhesion kinase,FAK)-P53信号通路变化情况。结果与sh-NC组比较,sh-NC+AngⅡ组迁移细胞数量、黏附细胞数量、小管形成数量显著降低,细胞凋亡率、整合素β1、磷酸化FAK(p-FAK)/FAK及P53蛋白表达显著增高,差异有统计学意义(P<0.05)。与sh-NC+AngⅡ组比较,sh-ABI3BP+AngⅡ组迁移细胞数量[(88.67±8.33)个vs(62.33±7.37)个]、黏附细胞数量[(104.33±6.03)个vs(68.33±10.05)个]、小管形成数量[(36.33±3.21)个vs(19.33±3.06)个]显著增高,细胞凋亡率、整合素β1、p-FAK/FAK及P53蛋白表达水平显著降低,差异有统计学意义(P<0.05)。结论AngⅡ可上调ABI3BP表达,敲低ABI3BP基因表达可改善AngⅡ诱导的内皮祖细胞功能障碍,其机制可能与抑制整合素β1-FAK-P53信号通路有关。展开更多
Objective.To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty. Methods. In rat aortic artery restenosis model produced by denudation of aortic ...Objective.To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty. Methods. In rat aortic artery restenosis model produced by denudation of aortic endothelia,we observed changes of endothelin(ET),angiotensin II(AII),calcitonin gene-related peptide(CGRP)and adrenomedullin(Adm)in plasma and aorta with radioimmunoassay and expression of hypertension-related gene(HRG-1)with semi-quantitative RT-PCR,and studied the effects of these peptides on intimal hyperplasia,intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore,in cultured cells,we studied the effects of these peptides on vascular smooth muscle cell(VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats with 3H-TdR incorporation and RT-PCR respectively. Results. After angioplasty,the levels of ET and AII in plasma and aorta significantly increased,accompanied with VSMC proliferation and neointima hyperplasia. On day 10 after angioplasty,the levels of ET in plasma and aorta increased by 69% and 124% respectively,compared with sham group(P<0.01);and the level of aortic AII increased by 80%(P< 0.01). Antiserum against ET or inhibitors of angiotensin converting enzyme(ACE)could significantly inhibit the proliferation of VSMC and neointima formation. Compared with the sham group,on day 3 after angioplasty,the CGRP levels in plasma and aorta increased by 64% and 89% respectively(P< 0.01)and the Adm levels in plasma and tissue increased by 129% and 102% respectively(P< 0.01). On day 10,intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima forma-tion induced by balloon aortic injury(by 66% and 79% respectively,P< 0.01). In addition,ET and AII attenuated the expression of HRG-1 in aorta and stimulated mitogen-activated protein kinase(MAPK)activity,while CGRP and Adm potentiated the expression of HRG-1 and inhibited MAPK.Conclusions. ET and AII can stimulate the proliferation of injured intima while CGRP and Adm have an anti-hyperplasia effect after angioplasty. These 4 peptides are involved in the regulation of VSMC proliferation and affect the development of vascular restenosis by regulating the expression of HRG-1 and MAPK activity.展开更多
基金This research was supported by the National Natural Sciences Foundation (No.39730220).
文摘Objective. To study the effect of interleukin 10 (IL- 10) on the angiotensin II (AngII) stimulated rat VSMC proliferation and collagen secretion, and furthermore, explore its mechanism. Methods. On cultured VSMC of rat, 3H- thymine (3H- TdR) and 3H- proline incorporations were used to evaluate the DNA and collagen synthesis, respectively. Western blot and immunoprecipitation were applied to assay the expression and activity of focal adhesion kinase (FAK), respectively. Results. IL- 10 (10－ 8～ 10－ 10g/ml) inhibited the increase of 3H- TdR and 3H- proline incorporation as well as FAK activity, which was induced by 10－ 7mol/L AngII (P< 0.05 or P< 0.01). IL- 10 also obviously downregulated the synthesis and secretion of collagen by AngII stimulated VSMC. But there was no difference in the protein expression of FAK among all the groups (P >0.05). Conclusion. IL- 10 antagonizes the VSMC proliferation and collagen synthesis by regulating FAK activity stimulated by AngII.
基金This work was supported by the research grants from National Natural Sciences Foundation of China(No. 39730220)
文摘The present study investigated the role of calcineurin in angiotensin II(AngII)- induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII- treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H- leucine incorporation; atrial natriuretic factor(ANF) mRNA level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13％ ,57％ (P Conclusion. During AngII- induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII- induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII- induced myocardial hypertrophy of rats.
文摘Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit＋ bosentan group and Nit＋ losartan group. Nitroglycerin tolerance was induced by 2- day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg－ 1· d－ 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg－ 1· d－ 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit＋ losartan group and Nit＋ bosentan group compared with Nit group [(31.95± 4.45 )％ vs (21.00± 3.69 )％ , P< 0.01 and (33.18± 6.16 )％ vs (21.00± 3.69 )％ , P< 0.01 ,respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50％ of the maximal response to SNP) was found in tolerant group[(34± 10) nmol/ L,P < 0.01 .The ET- 1 amounts in plasma and vascular tissue were markedly increased by 54％ and 60％ in Nit group compared with those in control group(P< 0.01).The ET- 1 amounts in plasma and vascular tissue were decreased by 30％ and 37％ in Nit＋ losartan group compared with those in Nit group (P< 0.01). Conclusion. Endothelin receptor antagonist and angiotensinⅡ receptor antagonist could prevent against the Nit tolerance .
基金the National Key Research and Develop Program of China(2017YFC0908802).
文摘Objective To evaluate the effect of angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)therapy on the prognosis of patients with atrial fibrillation(AF).Methods A total of 1,991 AF patients from the AF registry were divided into two groups according to whether they were treated with ACEI/ARB at recruitment.Baseline characteristics were carefully collected and analyzed.Logistic regression was utilized to identify the predictors of ACEI/ARB therapy.The primary endpoint was all-cause mortality,while the secondary endpoints included cardiovascular mortality,stroke and major adverse events(MAEs)during the one-year follow-up period.Univariable and multivariable Cox regression were performed to identify the association between ACEI/ARB therapy and the one-year outcomes.Results In total,759 AF patients(38.1%)were treated with ACEI/ARB.Compared with AF patients without ACEI/ARB therapy,patients treated with ACEI/ARB tended to be older and had a higher rate of permanent AF,hypertension,diabetes mellitus,heart failure(HF),left ventricular ejection fraction(LVEF)<40%,coronary artery disease(CAD),prior myocardial infarction(MI),left ventricular hypertrophy,tobacco use and concomitant medications(all P<0.05).Hypertension,HF,LVEF<40%,CAD,prior MI and tobacco use were determined to be predictors of ACEI/ARB treatment.Multivariable analysis showed that ACEI/ARB therapy was associated with a significantly lower risk of one-year all-cause mortality[hazard ratio(HR)(95%CI):0.682(0.527-0.882),P=0.003],cardiovascular mortality[HR(95%CI):0.713(0.514-0.988),P=0.042]and MAEs[HR(95%CI):0.698(0.568-0.859),P=0.001].The association between ACEI/ARB therapy and reduced mortality was consistent in the subgroup analysis.Conclusions In patients with AF,ACEI/ARB was related to significantly reduced one-year all-cause mortality,cardiovascular mortality and MAEs despite the high burden of cardiovascular comorbidities.
基金This work was supported by the research grants from the National Natural Sciences Foundation of China (39870355).This work was originally published in National Medical Journal of China(2001 18: 162-167)in Chinese.
文摘Objective.To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty. Methods. In rat aortic artery restenosis model produced by denudation of aortic endothelia,we observed changes of endothelin(ET),angiotensin II(AII),calcitonin gene-related peptide(CGRP)and adrenomedullin(Adm)in plasma and aorta with radioimmunoassay and expression of hypertension-related gene(HRG-1)with semi-quantitative RT-PCR,and studied the effects of these peptides on intimal hyperplasia,intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore,in cultured cells,we studied the effects of these peptides on vascular smooth muscle cell(VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats with 3H-TdR incorporation and RT-PCR respectively. Results. After angioplasty,the levels of ET and AII in plasma and aorta significantly increased,accompanied with VSMC proliferation and neointima hyperplasia. On day 10 after angioplasty,the levels of ET in plasma and aorta increased by 69% and 124% respectively,compared with sham group(P<0.01);and the level of aortic AII increased by 80%(P< 0.01). Antiserum against ET or inhibitors of angiotensin converting enzyme(ACE)could significantly inhibit the proliferation of VSMC and neointima formation. Compared with the sham group,on day 3 after angioplasty,the CGRP levels in plasma and aorta increased by 64% and 89% respectively(P< 0.01)and the Adm levels in plasma and tissue increased by 129% and 102% respectively(P< 0.01). On day 10,intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima forma-tion induced by balloon aortic injury(by 66% and 79% respectively,P< 0.01). In addition,ET and AII attenuated the expression of HRG-1 in aorta and stimulated mitogen-activated protein kinase(MAPK)activity,while CGRP and Adm potentiated the expression of HRG-1 and inhibited MAPK.Conclusions. ET and AII can stimulate the proliferation of injured intima while CGRP and Adm have an anti-hyperplasia effect after angioplasty. These 4 peptides are involved in the regulation of VSMC proliferation and affect the development of vascular restenosis by regulating the expression of HRG-1 and MAPK activity.
