Caveolin-1 is important for nitric oxide-mediated angiogenesis in fibrin gels with human umbilical vein endothelial cells

作     者：Yi-ming PAN Yong-zhong YAO Zhang-hua ZHU Xi-tai SUN Yu-dong QIU Yi-tao DING~2 Department of Hepatobiliary Surgery,Drum Tower Hospital,Medical College of Nanjing University and Hepatobiliary Institute of Nanjing University,Nanjing 210008,China 

作者机构：DepartmentofHepatobiliarySurgeryDrumTowerHospitalMedicalCollegeofNanjingUniversityandHepatobiliaryInstituteofNanjingUniversityNanjing210008China 

出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))

年 卷 期：2006年第27卷第12期

页      面：1567-1574页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：Project supported by grants from the Personnel Department of Jiangsu Province China(№ C-2002-012) 

主　　题：caveolin-1 angiogenesis nitric oxide vascular endothelial growth factor 

摘      要：Aim:The role of caveolin-1(Cav-1)in angiogenesis remains poorly *** endothelial nitric oxide(NO)synthase(eNOS),a caveolin-interacting protein,was demonstrated to play a predominant role in vascular endothelial growth fac-tor(VEGF)-induced *** purpose of our study was to examine therole of Cav-1 and the eNOS complex in NO-mediated ***:Human umbilical vein endothelial cells(HUVEC)were isolated and cultured in 3-Dfibrin gels to form capillary-like tubules by VEGF *** expression ofCav-1 and eNOS was detected by semiquantitative *** HUVEC weretreated with antisense oligonucleotides to downregulate Cav-1 *** and non-infected HUVEC were cultured in fibrin gels in the presenceor absence of VEGF(20 ng/mL)and N~G-nitro-L-arginine methyl ester(L-NAME;5 mmol/L).NO was measured using a NO assay kit and capillary-like tubules werequantified by tubule formation index using the Image J ***:RT-PCRanalysis revealed that Cav-1 levels steadily increased in a time-dependent mannerand reached their maximum after 5d of incubation,but there were no obviouschanges in eNOS mRNA expression in response to VEGF in the fibrin gel ***(20 ng/mL)can promote NO production and the formation of capillary-liketubules,and this promoting effect of VEGF was blocked by the addition ofL-NAME(5 mmol/L).When transduced HUVEC with the antisense Cav-1 oligo-nucleotides were plated in the fibrin gels,the capillary-like tubules were signifi-cantly fewer than those of the non-infected *** capillary-like tubules forma-tion and NO production of transduced HUVEC with the antisense Car-1 oligo-nucleotides cultured in fibrin gels showed no responses to the addition of VEGF(20 ng/mL)and L-NAME(5.0 mmol/L).Conclusion:NO was a critical angiogenicmediator in this ***-1 was essential for NO-mediated angiogenesis andmay be an important target of anti-angiogenesis therapy.