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

ABSTRACT AIM: The role of caveolin-1 (Cav-1) in angiogenesis remains poorly understood. The endothelial nitric oxide (NO) synthase (eNOS), a caveolin-interacting protein, was demonstrated to

play a predominant role in vascular endothelial growth factor (VEGF) -induced angiogenesis. The purpose of our study was to examine the role of Cav-1 and the eNOS complex in NO-mediated

angiogenesis. METHODS: Human umbilical vein endothelial cells (HUVEC) were isolated and cultured in 3-D fibrin gels to form capillary-like tubules by VEGF stimulation. The expression of

Cav-1 and eNOS was detected by semiquantitative RT-PCR. The HUVEC were treated with antisense oligonucleotides to downregulate Cav-1 expression. Both transduced and non-infected HUVEC were

cultured in fibrin gels in the presence or 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 were quantified by tubule formation index using the Image J program. RESULTS: RT-PCR analysis revealed that Cav-1 levels steadily increased in a time-dependent manner and reached

their maximum after 5 d of incubation, but there were no obvious changes in eNOS mRNA expression in response to VEGF in the fibrin gel model. VEGF (20 ng/mL) can promote NO production and

the formation of capillary-like tubules, and this promoting effect of VEGF was blocked by the addition of _L_-NAME (5 mmol/L). When transduced HUVEC with the antisense Cav-1 oligonucleotides

were plated in the fibrin gels, the capillary-like tubules were significantly fewer than those of the non-infected cells. The capillary-like tubules formation and NO production of

transduced HUVEC with the antisense Cav-1 oligonucleotides 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 angiogenic mediator in this model. Cav-1 was essential for NO-mediated angiogenesis and may be an important target of anti-angiogenesis therapy. SIMILAR CONTENT BEING VIEWED BY

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2004; 95: 154–61. Article  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Hepatobiliary Surgery, Drum Tower Hospital, Medical College of

Nanjing University and Hepatobiliary Institute of Nanjing University, Nanjing, 210008, China Yi-ming Pan, Yong-zhong Yao, Zhang-hua Zhu, Xi-tai Sun, Yu-dong Qiu & Yi-tao Ding Authors *

Yi-ming Pan View author publications You can also search for this author inPubMed Google Scholar * Yong-zhong Yao View author publications You can also search for this author inPubMed Google

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author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Yi-tao Ding. ADDITIONAL INFORMATION Project supported by grants from the Personnel Department of Jiangsu Province,

China (No C-2002-012). RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Pan, Ym., Yao, Yz., Zhu, Zh. _et al._ Caveolin-1 is important for nitric

oxide-mediated angiogenesis in fibrin gels with human umbilical vein endothelial cells. _Acta Pharmacol Sin_ 27, 1567–1574 (2006). https://doi.org/10.1111/j.1745-7254.2006.00462.x Download

citation * Received: 21 July 2006 * Accepted: 08 August 2006 * Issue Date: 01 December 2006 * DOI: https://doi.org/10.1111/j.1745-7254.2006.00462.x SHARE THIS ARTICLE Anyone you share the

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Nature SharedIt content-sharing initiative KEYWORDS * caveolin-1 * angiogenesis * nitric oxide * vascular endothelial growth factor