ADVANCE IN VASCULAR ENDOTHELIUM GROWTH FACTOR AND VASCULAR ENDOTHELIUM GROWTH FACTOR GENE THERAPY FOR PATIENTS WITH LIMB ISCHEMIA_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

TU Bing

Department of General Surgery, The First Affiliated Hospital, West China University of Medical Sciences, Chengdu 610041;

Corresponding author：

Keywords：

Vascular endothelium factor Limb ischemia Gene therapy

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Objective To review the studies on vascular endothelium growth factor (VEGF) gene therapy for patients with chronic critical limb ischemia.
Methods Advance in molecular biology of VEGF, mechanism of new vessel formation induced by VEGF and achievement of improving blood flow in patients with critical limb ischemia due to VEGF expressed by gene transfer in recent years has been reviewed in this article.
Results Preclinical studies showed that VEGF can stimulate the development of collateral arteries in animals with limb ischemia, a concept called “therapeutic angiogenesis”, clinical results demonstrated that VEGF expressed by gene transfer can promote new vessel formation in patients with critical limb ischemia and improve significantly the prognosis for them.
Conclusion VEGF gene transfer provide a novel treatment strategy for patients with critical limb ischemia, who neither had favorable response to phamarcological treatment nor were suitable for surgical reconstruction or revascularization.

Citation： TU Bing,JIN Liren.. ADVANCE IN VASCULAR ENDOTHELIUM GROWTH FACTOR AND VASCULAR ENDOTHELIUM GROWTH FACTOR GENE THERAPY FOR PATIENTS WITH LIMB ISCHEMIA. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2000, 7(3): 202-204. doi: Copy

1.	European working group on critical leg iscemia. Second european consensus document on chronic critical leg ischemia 〔Ｊ〕. Circulation, 1991; 84(Suppl Ⅳ)∶Ⅳ1.
2.	Dormancly J, Mahir M, Ascady G, et al. Fate of the patient with chronic leg ischemia 〔Ｊ〕. J Cardiovasc Surg, 1989; 30(1)∶50.
3.	Isner JM, Rosenfield K. Redefining the treatment of perpheral artery disease 〔Ｊ〕. Circulation, 1993; 88(4)∶1534.
4.	Hckel M, Schlenger K, Doctrow S, et al. Therapeutic angiogenesis 〔Ｊ〕. Arch Surg, 1993; 128(4)∶423.
5.	Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparinbinding growth factor specific for vascular endothelial cells 〔Ｊ〕. Biochem Biophys Res Commun, 1989; 161(2)∶851.
6.	Ferrara N, Houck K, Jakeman L, et al. Molecular and biological properties of the vascular endothelial growth factor family proteins 〔Ｊ〕. Endocrine Reviews, 1992; 13(1)∶18.
7.	Mandriota SJ, Seghezzi G, Vassalli TD, et al. Vascular endothelial growth factor increase urokinase receptor expression in vascular endothelial cells 〔Ｊ〕. J Bio Chem, 1995; 270(17)∶9707.
8.	Takeshita S, Zheng LP, Borgi E, et al. Therapeutic angiogenesis: a single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model 〔Ｊ〕. J Clin Invest, 1994; 93(2)∶662.
9.	Takeshita S, Pu LQ, Stein LA, et al. Intramuscular administration of vascular endothelial growth factor induces dosedependent collateral artery augmentation in a rabbit model of chronic limb ischemia 〔Ｊ〕. Circulation, 1994; 90(57)∶Ⅱ-228.
10.	Wolff JA, Malone RW, Williams P, et al. Direct gene transfer into mouse muscle in vivo 〔Ｊ〕. Science, 1990; 247(4949)∶1465.
11.	Nable EG, Plautz G, Nable GZ, et al. Sitespecific gene expression in vivo by direct gene transfer into the arterial wall 〔Ｊ〕. Science, 1990; 249(4974)∶1285.
12.	Isner JM, Walsh K, Symes J, et al. Arterial gene therapy for theraputic angiogenesis in patients with peripheral artery disease 〔Ｊ〕. Circulation, 1995; 91(11)∶2687.
13.	Isner JM, Pieczek A, Schainfeld R, et al. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischemic limb 〔Ｊ〕. Lancet, 1996; 348(9024)∶370.
14.	Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia 〔Ｊ〕. Circulation, 1998; 97(12)∶1114.
15.	Takeshita S, Tsurumi Y, Couffinhal T, et al. Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo 〔Ｊ〕. Lab Invest, 1996; 75(4)∶487.
16.	Ferrara N, Winer J, Bunton T, et al. Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to chinese hamster ovary cells 〔Ｊ〕. J Clin Invest, 1992; 91(1)∶160.
17.	Aiello LP, Avery AL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluids of patients with diabetic retinopathy and other retinal disorder 〔Ｊ〕. N Eng J Med, 1994; 331(22)∶1480.

1. European working group on critical leg iscemia. Second european consensus document on chronic critical leg ischemia 〔Ｊ〕. Circulation, 1991; 84(Suppl Ⅳ)∶Ⅳ1.
2. Dormancly J, Mahir M, Ascady G, et al. Fate of the patient with chronic leg ischemia 〔Ｊ〕. J Cardiovasc Surg, 1989; 30(1)∶50.
3. Isner JM, Rosenfield K. Redefining the treatment of perpheral artery disease 〔Ｊ〕. Circulation, 1993; 88(4)∶1534.
4. Hckel M, Schlenger K, Doctrow S, et al. Therapeutic angiogenesis 〔Ｊ〕. Arch Surg, 1993; 128(4)∶423.
5. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparinbinding growth factor specific for vascular endothelial cells 〔Ｊ〕. Biochem Biophys Res Commun, 1989; 161(2)∶851.
6. Ferrara N, Houck K, Jakeman L, et al. Molecular and biological properties of the vascular endothelial growth factor family proteins 〔Ｊ〕. Endocrine Reviews, 1992; 13(1)∶18.
7. Mandriota SJ, Seghezzi G, Vassalli TD, et al. Vascular endothelial growth factor increase urokinase receptor expression in vascular endothelial cells 〔Ｊ〕. J Bio Chem, 1995; 270(17)∶9707.
8. Takeshita S, Zheng LP, Borgi E, et al. Therapeutic angiogenesis: a single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model 〔Ｊ〕. J Clin Invest, 1994; 93(2)∶662.
9. Takeshita S, Pu LQ, Stein LA, et al. Intramuscular administration of vascular endothelial growth factor induces dosedependent collateral artery augmentation in a rabbit model of chronic limb ischemia 〔Ｊ〕. Circulation, 1994; 90(57)∶Ⅱ-228.
10. Wolff JA, Malone RW, Williams P, et al. Direct gene transfer into mouse muscle in vivo 〔Ｊ〕. Science, 1990; 247(4949)∶1465.
11. Nable EG, Plautz G, Nable GZ, et al. Sitespecific gene expression in vivo by direct gene transfer into the arterial wall 〔Ｊ〕. Science, 1990; 249(4974)∶1285.
12. Isner JM, Walsh K, Symes J, et al. Arterial gene therapy for theraputic angiogenesis in patients with peripheral artery disease 〔Ｊ〕. Circulation, 1995; 91(11)∶2687.
13. Isner JM, Pieczek A, Schainfeld R, et al. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischemic limb 〔Ｊ〕. Lancet, 1996; 348(9024)∶370.
14. Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia 〔Ｊ〕. Circulation, 1998; 97(12)∶1114.
15. Takeshita S, Tsurumi Y, Couffinhal T, et al. Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo 〔Ｊ〕. Lab Invest, 1996; 75(4)∶487.
16. Ferrara N, Winer J, Bunton T, et al. Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to chinese hamster ovary cells 〔Ｊ〕. J Clin Invest, 1992; 91(1)∶160.
17. Aiello LP, Avery AL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluids of patients with diabetic retinopathy and other retinal disorder 〔Ｊ〕. N Eng J Med, 1994; 331(22)∶1480.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

ADVANCE IN VASCULAR ENDOTHELIUM GROWTH FACTOR AND VASCULAR ENDOTHELIUM GROWTH FACTOR GENE THERAPY FOR PATIENTS WITH LIMB ISCHEMIA

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