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Gene therapy of hypertensive vascular injury

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Abstract

Hypertension and vascular injury usually require prolonged treatment, and compliance is a key to efficacy for pharmacologically-based antihypertensive therapy. Gene therapy has the potential to be long lasting, with few side effects. Recent studies have provided promising results, in which hypertension can be treated by either augmentation of vasodilation or inhibition of vasoconstriction through gene transfer in experimental models. Gene transfer is also becoming useful for the study of mechanisms of physiologic and pathophysiologic conditions, including hypertension. In this mini-review, we summarize some recent studies in this area of research, and suggest some areas where progress is needed t advance the research toward gene therapy.

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References and Recommended Reading

  1. Heistad DD, Faraci FM: Gene therapy for cerebral vascular disease. Stroke 1996, 27:1688–1693.

    PubMed  CAS  Google Scholar 

  2. Phillips MI: Is gene therapy for hypertension possible? Hypertension 1999, 33:8–13. This recent review summarizes evidence suggesting that gene therapy for hypertension is possible.

    PubMed  CAS  Google Scholar 

  3. Daniels V, Casey A: Antihypertensives. Phys Med Rehabil Clin North Am 1999, 10:319–335.

    CAS  Google Scholar 

  4. de Gasparo M, Levens N: Does blockade of angiotensin II receptors offer clinical benefits over inhibition of angiotensin-converting enzyme? Pharmacol Toxicol 1998, 82:257–271.

    Article  PubMed  Google Scholar 

  5. Dzau VJ, Gibbons GH, Morishita R, Pratt RE: New perspectives in hypertension research, potentials of vascular biology. Hypertension 1994, 23:1132–1140.

    PubMed  CAS  Google Scholar 

  6. Lifton RP: Molecular genetics of human blood pressure variation. Science 1996, 272:676–680.

    Article  PubMed  CAS  Google Scholar 

  7. Zabner J, Ramsey BW, Meeker DP, et al.: Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis. J Clin Invest 1996, 97:1504–1511.

    PubMed  CAS  Google Scholar 

  8. Allikmets K, Parik T, Viigimaa M: The renin-angiotensin system in essential hypertension: associations with cardiovascular risk. Blood Press 1999, 8:70–78.

    Article  PubMed  CAS  Google Scholar 

  9. Schiffrin EL: Role of endothelin-1 in hypertension. Hypertension 1999, 34:876–881.

    PubMed  CAS  Google Scholar 

  10. Margolius HS: Kallikreins, kinins and cardiovascular diseases: a short review. Biol Res 1998, 31:135–141.

    PubMed  CAS  Google Scholar 

  11. Ationu A, Boateng S: The role of natriuretic peptides in cardiovascular disorders and human cardiac allografts [review]. Int J Mol Med 1998, 2:235–239.

    PubMed  CAS  Google Scholar 

  12. Huang PL, Huang Z, Mashimo H, et al.: Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 1995, 377:239–242.

    Article  PubMed  CAS  Google Scholar 

  13. Vanhoutte PM: Endothelial dysfunction in hypertension. J Hypertens 1996, 14:S83-S93.

    Article  CAS  Google Scholar 

  14. Luscher TF: The endothelium and cardiovascular disease: a complex relation. N Engl J Med 1994, 330:1081–1083.

    Article  PubMed  CAS  Google Scholar 

  15. Nakazono K, Watanabe N, Matsumo K, et al.: Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci USA 1991, 88:10045–10048.

    Article  PubMed  CAS  Google Scholar 

  16. McIntyre M, Bohn DF, Dominiczak AF: Endothelial function in hypertension: the role of superoxide anion. Hypertension 1999, 34:539–545. This recent review summarizes the contribution of oxidative stress in general and superoxide in particuler to hypertension.

    PubMed  CAS  Google Scholar 

  17. Faraci FM, Heistad DD: Regulation of cerebral blood vessels by humoral and endothelium-dependent mechanisms: update on humoral regulation of vascular tone. Hypertension 1991, 17:917–922.

    PubMed  CAS  Google Scholar 

  18. Wang C, Chao L, Chao J: Direct gene delivery of human tissue kallikrein reduces blood pressure in spontaneously hypertensive rats. J Clin Invest 1995, 95:1710–1716.

    PubMed  CAS  Google Scholar 

  19. Zhang JJ, Chao L, Chao J: Adenovirus-mediated kallikrein gene delivery reduces aortic thickening and stroke-induced death rate in Dahl salt-sensitive rats. Stroke 1999, 30:1925–1932.

    PubMed  CAS  Google Scholar 

  20. Chao J, Zhang JJ, Lin KF, Chao L: Adenovirus-mediated kallikrein gene delivery reverses salt-induced renal injury in Dahl salt-sensitive rats. Kidney Int 1998, 54:1250–1260.

    Article  PubMed  CAS  Google Scholar 

  21. Lin KF, Chao J, Chao L: Human atrial natriuretic peptide gene delivery reduces blood pressure in hypertensive rats. Hypertension 1995, 26:847–853.

    PubMed  CAS  Google Scholar 

  22. Lin KF, Chao J, Chao L: Atrial natriuretic peptide gene delivery reduces stroke-induced mortality rate in Dahl salt-sensitive rats. Hypertension 1999, 33:219–224.

    PubMed  CAS  Google Scholar 

  23. Lin KF, Chao L, Chao J: Prolonged reduction of high blood pressure with human nitric oxide synthase gene delivery. Hypertension 1997, 30:307–313.

    PubMed  CAS  Google Scholar 

  24. Gyurko R, Wielbo D, Phillips MI: Antisense inhibition of AT1 receptor mRNA and angiotensinogen mRNA in the brain of spontaneously hypertensive rats reduces hypertension of neurogenic origin. Regul Pept 1993, 49:167–174.

    Article  PubMed  CAS  Google Scholar 

  25. Phillips MI, Wielbo D, Gyurko R: Antisense inhibition of hypertension: a new strategy for renin-angiotensin candidate genes. Kidney Int 1994, 46:1554–1556.

    Article  PubMed  CAS  Google Scholar 

  26. Wielbo D, Sernia C, Gyurko R, Phillips MI: Antisense inhibition of hypertension in the spontaneously hypertensive rat. Hypertension 1995, 25:314–319.

    PubMed  CAS  Google Scholar 

  27. Tomita N, Morishita R, Higaki J, et al.: Transient decrease in high blood pressure by in vivo transfer of antisense oligodeoxynucleotides against rat angiotensinogen. Hypertension 1995, 26:131–136.

    PubMed  CAS  Google Scholar 

  28. Wielbo D, Simon A, Phillips MI, Toffolo S: Inhibition of hypertension by peripheral administration of antisense oligonucleotides. Hypertension 1996, 28:147–151.

    PubMed  CAS  Google Scholar 

  29. Makino N, Sugano M, Ohtsuka S, Sawada S: Intravenous injection with antisense oligodeoxynucleotides against angiotensinogen decreases blood pressure in spontaneosly hypertensive rats. Hypertension 1998, 31:1166–1170.

    PubMed  CAS  Google Scholar 

  30. Phillips MI, Mohuczy-Dominiak D, Coffey M, et al.: Prolonged reduction of high blood pressure with an in vivo, nonpathogenic, adeno-associated viral vector delivery of AT1-R mRNA antisense. Hypertension 1997, 29:374–380.

    PubMed  CAS  Google Scholar 

  31. Kotovich MJ, Gelband, CH, Reaves P, et al.: Reversal of hypertension by angiotensin II type 1 receptor antisense gene therapy in the adult SHR. Am J Physiol 1999, 277:H1260-H1264.

    Google Scholar 

  32. Iyer SN, Lu D, Katovich M, Raizada MK: Chronic control of high blood pressure in the spontaneously hypertensive rat by delivery of angiotensin type 1 receptor antisense. Proc Natl Acad Sci USA 1996, 93:9960–9965.

    Article  PubMed  CAS  Google Scholar 

  33. Martens JR, Reaves PY, Lu D, et al.: Prevention of renovascular and cardiac pathophysiological changes in hypertension by angiotensin II type I receptor antisense gene therapy Proc Natl Acad Sci USA 1998, 95:2664–2669.

    Article  PubMed  CAS  Google Scholar 

  34. Wang H, Katovich MJ, Gelband CH, et al.: Sustained inhibition of angiotensin I-converting enzyme (ACE) expression and long-term antihypertensive action by virally mediated delivery of ACE antisense cDNA. Circ Res 1999, 85:614–622. This paper showed convincingly the effectiveness of retrovirus-mediated antisense gene therapy in cultured endothelial cells and SHR neonates.

    PubMed  CAS  Google Scholar 

  35. Raizada MK, Katovich MJ, Wang, H, et al.: Is antisense gene therapy a step in the right direction in the control of hypertension? Am J Physiol 1999, H423–H432. This review provides a nice introduction to physicians and physiologists of antisense gene transfer for hypertension.

  36. Ooboshi H, Rios CD, Heistad DD: Novel methods for adenovirus-mediated gene transfer to blood vessels in vivo. Mol Cell Biochem 1997, 172:37–46.

    Article  PubMed  CAS  Google Scholar 

  37. Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA: Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 1993, 87:1468–1474.

    PubMed  CAS  Google Scholar 

  38. Omar HA, Cherry PD, Motelliti MP, et al.: Inhibition of coronary artery superoxide dismutase attenuates endotheliumdependent and -independent nitrovasodilator relaxation. Circ Res 1991, 69:601–608.

    PubMed  CAS  Google Scholar 

  39. Taddei S, Virdis A, Ghiadoni L, et al.: Vitamin C improves endothelium-dependent vasodilatation by restoring nitric oxide activity in essential hypertension. Circulation 1998, 97:2222–2229.

    PubMed  CAS  Google Scholar 

  40. Ooboshi H, Chu Y, Rios CD, et al.: Altered vascular function after adenovirus-mediated overexpression of endothelial nitric oxide synthase. Am J Physiol 1997, 273:H265-H270. This paper showed the first evidence that adventitial gene transfer may be effective to alter vascular function.

    PubMed  CAS  Google Scholar 

  41. Onoue H, Tsutsui M, Smith L, et al.: Adventitial expression of recombinant endothelial nitric oxide synthase gene reverses vasoconstrictor effect of endothelin-1. J Cereb Blood Flow Metab 1999, 19:1029–1037.

    Article  PubMed  CAS  Google Scholar 

  42. Tsutsui M, Onoue H, Iida Y, et al.: Adventitia-dependen relaxations of canine basilar arteries transduced with recombinant eNOS gene Am J Physiol 1999, 276:H1846-H1852.

    PubMed  CAS  Google Scholar 

  43. Bech Laursen J, Rajagopalan S, Galis Z, et al.: Role of superoxide in angiotensin II-induced but not catecholamineinduced hypertension. Circulation 1997, 95:588–593.

    Google Scholar 

  44. Janssens SP, Bloch KD, Nong Z, et al.: Adenoviral-mediated transfer of the human endothelial nitric oxide synthase gene reduces acute hypoxic pulmonary vasoconstriction in rats. J Clin Invest 1996, 98:317–324.

    Article  PubMed  CAS  Google Scholar 

  45. Champion HC, Bivalacqua TJ, D’Souza FM, et al.: Gene transfer of endothelial nitric oxide synthase to the lung of the mouse in vivo: effect on agonist-induced and flow-mediated vascular responses. Circ Res 1999, 84:1422–1432.

    PubMed  CAS  Google Scholar 

  46. Tripathy SK, Black HB, Goldwasser E, Leiden JM: Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vector. Nat Med 1996, 2:545–550.

    Article  PubMed  CAS  Google Scholar 

  47. Qin L, Ding Y, Pahud DR, et al.: Promoter attenuation in gene therapy: interferon-gamma and tumor necrosis factor-alpha inhibit transgene expression. Hum Gene Ther 1997, 8:2019–2029.

    PubMed  CAS  Google Scholar 

  48. Christenson S, Lund D, Ooboshi H, et al.: Approaches to enhance expression after adenovirus-mediated gene transfer to the carotid artery. Endothelium 1999, 7:75–82.

    PubMed  CAS  Google Scholar 

  49. Rios CD, Chu Y, Davidson, BL, Heistad DD: Ten steps to gene therapy for vascular diseases. J Lab Clin Med 1998, 132:104–111.

    Article  PubMed  CAS  Google Scholar 

  50. Pratt RE, Dzau VJ: Genomics and hypertension: concepts potentials, and opportunities. Hypertension 1999, 33:238–247.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Cardiovascular Center, Department of Internal Medicine, University of Iowa College of Medicine, 52242, Iowa City, Iowa, USA

    Yi Chu PhD

  2. Cardiovascular Center, Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine, 52242, Iowa City, Iowa, USA

    Frank M. Faraci PhD

  3. Cardiovascular Center, Departments of Internal Medicine and Pharmacology, VA Medical Center, University of Iowa College of Medicine, 52242, Iowa City, Iowa, USA

    Donald D. Heistad MD

Authors
  1. Yi Chu PhD
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  2. Frank M. Faraci PhD
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  3. Donald D. Heistad MD
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Chu, Y., Faraci, F.M. & Heistad, D.D. Gene therapy of hypertensive vascular injury. Current Science Inc 2, 92–97 (2000). https://doi.org/10.1007/s11906-000-0065-4

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  • DOI: https://doi.org/10.1007/s11906-000-0065-4

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