• 重慶醫(yī)科大學附屬第一醫(yī)院血管外科（重慶400016）;

目的  討論使用外源性抗凝基因修飾內(nèi)皮細胞后襯里人工血管，使人工血管局部抗凝活性提高以及對內(nèi)皮細胞其他生物活性的影響等。
方法  復習近幾年的相關文獻，作綜述報道。
結果  內(nèi)皮細胞在轉染纖溶酶原激活物（tPA、uPA、Urokinase）、血栓調(diào)節(jié)蛋白（TM）和水蛭素（hirudin）等基因后，均使局部血管的抗凝活性增高，但同時也導致內(nèi)皮細胞粘附性、增殖功能下降。
結論  外源性基因能使內(nèi)皮細胞預襯的人工血管抗凝活性提高，但仍需進行深入研究。

引用本文： 戴毅,喬正榮,時德. 基因轉染內(nèi)皮細胞襯里人工血管的研究進展. 中國普外基礎與臨床雜志, 2004, 11(1): 86-88. doi: 復制

1. Dichek DA, Neville RF, Zwiebel JA, et al. Seeding of intravascular stents with genetically engineered endothelial cells [J]. Circulation, 1989; 80(5)∶1347.
2. Dichek DA, Anderson J, Kelly AB, et al. Enhanced in vivo antithrombotic effects of endothelial cells expressing recombinant plasminogen activators transduced with retroviral vectors [J]. Circulation, 1996; 93(2)∶301.
3. Dichek DA, Nussbaum O, Degen SJ, et al. Enhancement of the fibrinolytic activity of sheep endothelial cells by retroviral vectormediated gene transfer [J]. Blood, 1991; 77(3)∶533.
4. Ekhterae D, Stanley JC. Retroviral vectormediated transfer and expression of human tissue plasminogen activator gene in human endothelial and vascular smooth muscle cells [J]. J Vasc Surg, 1995; 21(6)∶953.
5. Wilson JM, Birinyi LK, Salomon RN, et al. Implantation of vascular grafts lined with genetically modified endothelial cells [J]. Science, 1989; 244(4910)∶1344.
6. Dichek DA, Lee SW, Nguyen NH. Characterization of recombinant plasminogen activator production by primate endothelial cells transduced with retroviral vectors [J]. Blood, 1994; 84(2)∶504.
7. Falk J, Townsend LE, Vogel LM, et al. Improved adherence of genetically modified endothelial cells to smalldiameter expanded polytetrafluoroethylene grafts in a canine model [J]. J Vasc Surg, 1998; 27(5)∶902.
8. Kopp CW, Grey ST, Siegel JB, et al. Expression of human thrombomodulin cofactor activity in porcine endothelial cells [J]. Transplantation, 1998; 66(2)∶244.
9. Waugh JM, Yuksel E, Li J, et al. Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model [J]. Circ Res, 1999; 84(1)∶84.
10. Waugh JM, LiHawkins J, Yuksel E, et al. Thrombomodulin overexpression to limit neointima formation [J]. Circulation, 2000; 102(3)∶332.
11. Lundell A, Kelly AB, Anderson J, et al. Reduction in vascular lesion formation by hirudin secreted from retrovirustransduced confluent endothelial cells on vascular grafts in baboons [J]. Circulation, 1999; 100(19)∶2018.
12. Rade JJ, Cheung M, Miyamoto S, et al. Retroviral vectormediated expression of hirudin by human vascular endothelial cells: implications for the design of retroviral vectors expressing biologically active proteins [J]. Gene Ther, 1999; 6(3)∶385.
13. Vassalli G, Dichek DA. Gene therapy for arterial thrombosis [J]. Cardiovasc Res, 1997; 35(3)∶459.
14. Dunn PF, Newman KD, Jones M, et al. Seeding of vascular grafts with genetically modified endothelial cells. Secretion of recombinant TPA results in decreased seeded cell retention in vitro and in vivo [J]. Circulation, 1996; 93(7)∶1439.
15. Huber TS, Welling TH, Sarkar R, et al. Effects of retroviralmediated tissue plasminogen activator gene transfer and expression on adherence and proliferation of canine endothelial cells seeded onto expanded polytetrafluoroethylene [J]. J Vasc Surg, 1995; 22(6)∶795.
16. Yu H, Wang Y, Eton D, et al. Dual cell seeding and the use of zymogen tissue plasminogen activator to improve cell retention on polytetrafluoroethylene grafts [J]. J Vasc Surg, 2001; 34(2)∶337.
17. Kimura H, Sakata Y, Hamada H, et al. In vivo retention of endothelial cells adenovirally transduced with tissuetype plasminogen activator and seeded onto expanded polytetrafluoroethylene [J]. J Vasc Surg, 2000; 32(2)∶353.
18. Jaklitsch MT, Biro S, Casscells W, et al. Transduced endothelial cells expressing high levels of tissue plasminogen activator have an unaltered phenotype in vitro [J]. J Cell Physiol, 1993; 154(1)∶207.
19. Baer RP, Whitehill TE, Sarkar R, et al. Retroviralmediated transduction of endothelial cells with the lac Z gene impairs cellular proliferation in vitro and graft endothelialization in vivo [J]. J Vasc Surg, 1996; 24(5)∶892.
20. Inaba M, Toninelli E, Vanmeter G, et al. Retroviral gene transfer: effects on endothelial cell phenotype [J]. J Surg Res, 1998; 78(1)∶31.
21. Rafii S, Dias S, Meeus S, et al. Infection of endothelium with E1(-)E4(+), but not E1(-)E4(-), adenovirus gene transfer vectors enhances leukocyte adhesion and migration by modulation of ICAM1, VCAM1, CD34, and chemokine expression [J]. Circ Res, 2001; 88(9)∶903.
  1. 1. Dichek DA, Neville RF, Zwiebel JA, et al. Seeding of intravascular stents with genetically engineered endothelial cells [J]. Circulation, 1989; 80(5)∶1347.
  2. 2. Dichek DA, Anderson J, Kelly AB, et al. Enhanced in vivo antithrombotic effects of endothelial cells expressing recombinant plasminogen activators transduced with retroviral vectors [J]. Circulation, 1996; 93(2)∶301.
  3. 3. Dichek DA, Nussbaum O, Degen SJ, et al. Enhancement of the fibrinolytic activity of sheep endothelial cells by retroviral vectormediated gene transfer [J]. Blood, 1991; 77(3)∶533.
  4. 4. Ekhterae D, Stanley JC. Retroviral vectormediated transfer and expression of human tissue plasminogen activator gene in human endothelial and vascular smooth muscle cells [J]. J Vasc Surg, 1995; 21(6)∶953.
  5. 5. Wilson JM, Birinyi LK, Salomon RN, et al. Implantation of vascular grafts lined with genetically modified endothelial cells [J]. Science, 1989; 244(4910)∶1344.
  6. 6. Dichek DA, Lee SW, Nguyen NH. Characterization of recombinant plasminogen activator production by primate endothelial cells transduced with retroviral vectors [J]. Blood, 1994; 84(2)∶504.
  7. 7. Falk J, Townsend LE, Vogel LM, et al. Improved adherence of genetically modified endothelial cells to smalldiameter expanded polytetrafluoroethylene grafts in a canine model [J]. J Vasc Surg, 1998; 27(5)∶902.
  8. 8. Kopp CW, Grey ST, Siegel JB, et al. Expression of human thrombomodulin cofactor activity in porcine endothelial cells [J]. Transplantation, 1998; 66(2)∶244.
  9. 9. Waugh JM, Yuksel E, Li J, et al. Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model [J]. Circ Res, 1999; 84(1)∶84.
  10. 10. Waugh JM, LiHawkins J, Yuksel E, et al. Thrombomodulin overexpression to limit neointima formation [J]. Circulation, 2000; 102(3)∶332.
  11. 11. Lundell A, Kelly AB, Anderson J, et al. Reduction in vascular lesion formation by hirudin secreted from retrovirustransduced confluent endothelial cells on vascular grafts in baboons [J]. Circulation, 1999; 100(19)∶2018.
  12. 12. Rade JJ, Cheung M, Miyamoto S, et al. Retroviral vectormediated expression of hirudin by human vascular endothelial cells: implications for the design of retroviral vectors expressing biologically active proteins [J]. Gene Ther, 1999; 6(3)∶385.
  13. 13. Vassalli G, Dichek DA. Gene therapy for arterial thrombosis [J]. Cardiovasc Res, 1997; 35(3)∶459.
  14. 14. Dunn PF, Newman KD, Jones M, et al. Seeding of vascular grafts with genetically modified endothelial cells. Secretion of recombinant TPA results in decreased seeded cell retention in vitro and in vivo [J]. Circulation, 1996; 93(7)∶1439.
  15. 15. Huber TS, Welling TH, Sarkar R, et al. Effects of retroviralmediated tissue plasminogen activator gene transfer and expression on adherence and proliferation of canine endothelial cells seeded onto expanded polytetrafluoroethylene [J]. J Vasc Surg, 1995; 22(6)∶795.
  16. 16. Yu H, Wang Y, Eton D, et al. Dual cell seeding and the use of zymogen tissue plasminogen activator to improve cell retention on polytetrafluoroethylene grafts [J]. J Vasc Surg, 2001; 34(2)∶337.
  17. 17. Kimura H, Sakata Y, Hamada H, et al. In vivo retention of endothelial cells adenovirally transduced with tissuetype plasminogen activator and seeded onto expanded polytetrafluoroethylene [J]. J Vasc Surg, 2000; 32(2)∶353.
  18. 18. Jaklitsch MT, Biro S, Casscells W, et al. Transduced endothelial cells expressing high levels of tissue plasminogen activator have an unaltered phenotype in vitro [J]. J Cell Physiol, 1993; 154(1)∶207.
  19. 19. Baer RP, Whitehill TE, Sarkar R, et al. Retroviralmediated transduction of endothelial cells with the lac Z gene impairs cellular proliferation in vitro and graft endothelialization in vivo [J]. J Vasc Surg, 1996; 24(5)∶892.
  20. 20. Inaba M, Toninelli E, Vanmeter G, et al. Retroviral gene transfer: effects on endothelial cell phenotype [J]. J Surg Res, 1998; 78(1)∶31.
  21. 21. Rafii S, Dias S, Meeus S, et al. Infection of endothelium with E1(-)E4(+), but not E1(-)E4(-), adenovirus gene transfer vectors enhances leukocyte adhesion and migration by modulation of ICAM1, VCAM1, CD34, and chemokine expression [J]. Circ Res, 2001; 88(9)∶903.