Abstract:To evaluate the role of nitric oxide in the biological effects of vascular endothelial growth factor (VEGF) and the possible mechanism of VEGF, the in vitro cultured vascular endothelial cells of rabbit aorta were divided into control group, VEGF-treated group and VEGF+ N-nitro-L-arginine methyl ester (L-NAME)-treated group. The absorbance (A) value of vascular endothelial cells and the levels of prostaglandin (PGI2), endothelin-1 (ET-1) and von Willebrand factor (vWF) in the supernatant were observed by water-soluble tetrazolium salt assay, radioimmunoassay and enzyme-linked immunosorbent assay. The A values and PGI2 in VEGF-treated group and VEGF+L-NAME-treated group were higher than those in control group (P<0.05 and P<0.01). The ET-1 and vWF were significantly decreased in VEGF-treated group and VEGF+L-NAME-treated group compared with the control (P<0.05 and P<0.01). These results indicate that VEGF could promote the proliferation and secretion of PGI2 and inhibit the secretion of ET-1 and vWF in vascular endothelial cells and that L-NAME could inhibit the effect of VEGF partially. Nitric oxide is an important mediator in the process of stimulating proliferation and regulating secretion of vascular endothelial cells by VEGF.
. Role of nitric oxide in biological effects of
vascular endothelial growth factor[J]. Front. Med., 2009, 3(3): 284-286.
Qigong LIU M D , Yan ZENG , Jiani LIU , Shan YE , Yongdong LI , Zaiying LU M D , . Role of nitric oxide in biological effects of
vascular endothelial growth factor. Front. Med., 2009, 3(3): 284-286.
Kusumanto Y H, van Weel V, Mulder N H, Smit A J, van den Dungen J J, Hooymans J M, Sluiter W J, Tio R A, Quax P H, Gans R O, Dullaart R P, Hospers G A. Treatment with intramuscular vascular endothelial growthfactor gene compared with placebo for patients with diabetes mellitusand critical limb ischemia: a double-blind randomized trial. Hum Gene Ther, 2006, 17(6): 683―691 doi: 10.1089/hum.2006.17.683
Qian H S, Liu P, Huw L Y, Orme A, Halks-Miller M, Hill S M, Jin F, Kretschmer P, Blasko E, Cashion L, Szymanski P, Vergona R, Harkins R, Yu J, Sessa W C, Dole W P, Rubanyi G M, Kauser K. Effective treatment of vascular endothelial growth factorrefractory hindlimb ischemia by a mutant endothelial nitric oxidesynthase gene. Gene Ther, 2006, 13(18): 1342―1350 doi: 10.1038/sj.gt.3302781
Testa U, Pannitteri G, Condorelli G L. Vascular endothelial growth factors in cardiovascularmedicine. J Cardiovasc Med (Hagerstown), 2008, 9(12): 1190―1221
Ylä-Herttuala S, Rissanen T T, Vajanto I, Hartikainen J. Vascular endothelial growth factors: biology and current status ofclinical applications in cardiovascular medicine. J Am Coll Cardiol, 2007, 49(10): 1015―1026 doi: 10.1016/j.jacc.2006.09.053
Bougioukas I, Didilis V, Ypsilantis P, Giatromanolaki A, Sivridis E, Lialiaris T, Mikroulis D, Simopoulos C, Bougioukas G. Intramyocardial injection of low-dose basic fibroblastgrowth factor or vascular endothelial growth factor induces angiogenesisin the infarcted rabbit myocardium. CardiovascPathol, 2007, 16(2): 63―68 doi: 10.1016/j.carpath.2006.08.006
Fuchs S, Dib N, Cohen B M, Okubagzi P, Diethrich E B, Campbell A, Macko J, Kessler P D, Rasmussen H S, Epstein S E, Kornowski R. A randomized, double-blind,placebo-controlled, multicenter, pilot study of the safety and feasibilityof catheter-based intramyocardial injection of AdVEGF121 in patientswith refractory advanced coronary artery disease. Catheter Cardiovasc Interv, 2006, 68(3): 372―378 doi: 10.1002/ccd.20859
Stewart D J, Hilton J D, Arnold J M, Gregoire J, Rivard A, Archer S L, Charbonneau F, Cohen E, Curtis M, Buller C E, Mendelsohn F O, Dib N, Page P, Ducas J, Plante S, Sullivan J, Macko J, Rasmussen C, Kessler P D, Rasmussen H S. Angiogenic gene therapy in patients with nonrevascularizableischemic heart disease: a phase 2 randomized, controlled trial ofAdVEGF(121) (AdVEGF121) versus maximum medical treatment. Gene Ther, 2006, 13(21): 1503―1511 doi: 10.1038/sj.gt.3302802
Liu Q G, Lu Z Y, Zhou H L, Yan J, Zhang W D. The mechanical study of vascular endothelialgrowth factor on the prevention of restenosis after angioplasty. J Tongji Med Univ, 2001, 21(3): 195―198
Deiner C, Schwimmbeck P L, Koehler I S, Loddenkemper C, Noutsias M, Nikol S, Schultheiss H P, Ylä-Herttuala S, Pels K. Adventitial VEGF165 gene transfer preventslumen loss through induction of positive arterial remodeling afterPTCA in porcine coronary arteries. Atherosclerosis, 2006, 189(1): 123―132 doi: 10.1016/j.atherosclerosis.2005.12.008
Sun Y M, Liu Q G, Zheng X Y. Effects of VEGF transduction through a Foley’scatheter on local vascular endothelial cell growth. Zhongguo Zuzhi Gongcheng Yanjiu Yu Linchuang Kangfu, 2008, 12(39): 7797―7800 (in Chinese)
Hedman M, Hartikainen J, Syvänne M, Stjernvall J, Hedman A, Kivelä A, Vanninen E, Mussalo H, Kauppila E, Simula S, Närvänen O, Rantala A, Peuhkurinen K, Nieminen M S, Laakso M, Ylä-Herttuala S. Safety and feasibility of catheter-based local intracoronary vascularendothelial growth factor gene transfer in the prevention of postangioplastyand in-stent restenosis and in the treatment of chronic myocardialischemia: phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation, 2003, 107(21): 2677―2683 doi: 10.1161/01.CIR.0000070540.80780.92
Hood J D, Meininger C J, Ziche M, Granger H J. VEGF upregulates ecNOS message, protein and NO production in humanendothelial cells. Am J Physiol, 1998, 274 (Heart Circ Physiol 43): H1054―1058
Ziche M, Morbidelli L, Choudhuri R, Zhang H T, Donnini S, Granger H J, Bicknell R. Nitric oxide synthase liesdownstream from vascular endothelial growth factor-induced but notbasic fibroblast growth factor-induced angiogenesis. J Clin Invest, 1997, 99(11): 2625―2634 doi: 10.1172/JCI119451