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Role of endothelin in diabetic vascular complications

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Abstract

Endothelin-1 (ET-1), a 21 amino acid peptide originally purified from conditioned medium of cultures of porcine aortic endothelial cells, is recognized as a product of many other cells as well. It is now known that there are three endothelin genes in the human genome (ET-1, ET-2, and ET-3). ET-1 and ET-2 are both strong vasoconstrictors, whereas ET-3 is a potentially weaker vasoconstrictor than the other two isoforms. Besides being the most potent vasoconstrictor yet known, ET-1 also acts as a mitogen on the vascular smooth muscle, and, thus, it may play a role in the development of vascular diseases. It is well known that accelerated angiopathy is a major complication in diabetes mellitus. As generalized endothelial cell damage is thought to occur in diabetic patients, ET-1, being released from the damaged endothelial cells, is able to make contact with the underlying vascular smooth muscle cells and thus could be one important cause of diabetic angiopathy. This article summarizes the reported literature of the role of ET-1 in the development of diabetic complications, with particular focus on the possible role of Et-1 in mediating the effects of angiotensin-converting enzyme inhibitors.

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References

  1. Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., and Mitsui, Y. (1988). Nature 332, 411–415.

    Article  PubMed  CAS  Google Scholar 

  2. Inoue, A., Yanagisawa, M., Kimura, S., Kasuya, Y., Miyauchi, T., Goto, K., and Masaki, T. (1989). Proc. Natl. Acad. Sci. USA 86, 2863–2867.

    Article  PubMed  CAS  Google Scholar 

  3. Takahashi, M., Matsushita, Y., Ijima, Y., and Tanzawa, K. (1993). J. Biol. Chem. 268, 21,394–21,398.

    CAS  Google Scholar 

  4. Emoto, N. and Yanagisawa, M. (1995). J. Biol. Chem. 270, 15,262–15,268.

    CAS  Google Scholar 

  5. Shimada, K., Takahashi, M., Ikeda, M., and Tanzawa, K. (1995). FEBS Lett. 371, 140–144.

    Article  PubMed  CAS  Google Scholar 

  6. Valdenaire, O., Rohrbacher, E., and Mattei, M. G. (1995). J. Biol. Chem. 270, 29,794–29,798.

    CAS  Google Scholar 

  7. Schweizer, A., Valdenaire, O., Nelbock, P., et al. (1997). Biochem. chem. J. 328, 871–877.

    CAS  Google Scholar 

  8. Valdenaire, O., Lepailleur-Enouf, D., Egidy, G., et al. (1999). Eur. J. Biochem. 264, 341–349.

    Article  PubMed  CAS  Google Scholar 

  9. Masaki, T. (1993). Endocr. Rev. 14, 256–268.

    Article  PubMed  CAS  Google Scholar 

  10. Takahashi, K., Jones, P. M., Kanse, S. M, et al. (1990). Gastroenterology 99, 1660–1667.

    PubMed  CAS  Google Scholar 

  11. Takahashi, K., Ghatei, M. A., Jones, P. M., et al. (1991). J. Clin. Endocrinol. Metab. 72, 693–699.

    PubMed  CAS  Google Scholar 

  12. Takahashi, K., Ghatei, M. A., Jones, P. M., et al. (1991). J. Cardiovasc. Pharmacol. 17(Suppl. 7), S101-S103.

    Article  PubMed  CAS  Google Scholar 

  13. Arai, H., Hori, S., Aramori, I., Ohkubo, H., and Nakanishi, S. (1990). Nature 348, 730–732.

    Article  PubMed  CAS  Google Scholar 

  14. Sakurai, T., Yanagisawa, M., Takuwa, Y., et al. (1990). Nature 348, 732–735.

    Article  PubMed  CAS  Google Scholar 

  15. Karne, S., Jayawickreme, C. K., and Lerner, M. R. (1993). J. Biol. Chem. 268, 19,126–19,133.

    CAS  Google Scholar 

  16. Moreland, S., McMullen, D. M., Delaney, C. L., Lee, V. G., and Hunt, J. T. (1992). Biochem. Biophys. Res. Commun. 184, 100–106.

    Article  PubMed  CAS  Google Scholar 

  17. Iwasaki, S., Homma, T., Matsuda, Y., and Kon, V. (1995). J. Biol. Chem. 270, 6997–7003.

    Article  PubMed  CAS  Google Scholar 

  18. Lam, H. C., Lee, J. K., and Lai, K. H. (2000). Endocrine 12, 77–80.

    Article  PubMed  CAS  Google Scholar 

  19. McMillen, M. A. and Sumpio, B. E. (1995). J. Am. Coll. surg. 180, 621–637.

    PubMed  CAS  Google Scholar 

  20. McMillan, D. E. (1984). Microcirc. Endothel. Lymphat. 1, 3–24.

    CAS  Google Scholar 

  21. Rubanyi, G. M. and Botelho, L. H. (1991). FASEB J. 5, 2713–2720.

    PubMed  CAS  Google Scholar 

  22. Nugent, A. G., McGurk, C., Hayes, J. R., and Johnstone, C. D. (1996). Diabetes 45, 105–107.

    Article  PubMed  CAS  Google Scholar 

  23. Sármán, B., Tóth, M., and Somogyi, A. (1998). Diabetes Metab. Rev. 14, 171–175.

    Article  PubMed  Google Scholar 

  24. Rohner, E. M. (1993). BMJ 307, 1195–1199.

    Google Scholar 

  25. Riva, C. E. and Loebl, M. (1977). Invest. Ophthalmol. 16, 586–592.

    Google Scholar 

  26. Chakravarthy, U. and Archer, D. B. (1992). Br. J. Ophthalmol. 76, 107, 108.

    PubMed  CAS  Google Scholar 

  27. Ye, X., Laties, A. M., and Stone, R. A. (1990). Invest. Ophthalmol. 31, 1731–1737.

    CAS  Google Scholar 

  28. Cogan, D. G., Toussaint, D., and Kuwabara, T. (1961). Arch. Ophthalmol. 63, 366–368.

    Google Scholar 

  29. Herman, I. M. and D'Amore, P. A. (1985). J. Cell Biol. 101, 43–52.

    Article  PubMed  CAS  Google Scholar 

  30. Takahashi, K., Brooks, R. A., Kanse, S. M., Ghatei, M. A., Kohner, E. M., and Bloom, S. R. (1989). Diabetes 38, 1200–1202.

    Article  PubMed  CAS  Google Scholar 

  31. Nyborg, N. C. B., Pieto, D., Benedito, S., and Nielsen, P. J. (1991). Invest. Ophthalmol. Vis. Sci. 32, 27–31.

    PubMed  CAS  Google Scholar 

  32. Chakravarthy, U., Gardiner, T. A., Anderson, P., Archer, D. B., and Trimble, E. R. (1992). Microvasc. Res. 43, 241–254.

    Article  PubMed  CAS  Google Scholar 

  33. Ogata, M., Naruse, M., Iwasaki, N., et al. (1998). J. Cardiovasc. Pharmacol. 31(Suppl. 1), S378,S379.

    Article  Google Scholar 

  34. Temple, R. C., Carrington, C. A., Luzio, S. D., Owens, D. R., Schneider, A. E., and Sobey, W. J. (1989). Lancet 1, 293–295.

    Article  PubMed  CAS  Google Scholar 

  35. Hattori, Y., Kasai, K., Nakamura, T., Emoto, T., and Shimoda, S. (1991). Metabolism 40, 165–169.

    Article  PubMed  CAS  Google Scholar 

  36. Ferri, C. and De-Mattia, G. (1995). Metabolism 44, 689, 690.

    Article  PubMed  CAS  Google Scholar 

  37. Metsärinne, K., Saijonomaa, O., Yki-Järvinen, H., and Fyhrquist, F. (1994). Metabolism 43, 878–882.

    Article  PubMed  Google Scholar 

  38. Yamauchi, T., Ohnaka, K., Takayanagi, R., Umeda, F., and Nawata, H. (1990). FEBS Lett. 267, 16–18.

    Article  PubMed  CAS  Google Scholar 

  39. Wolpert, H. A., Steen, S. N., Istfan, N. W., and Simonson, D. C. (1993). Metabolism 42, 1027–1030.

    Article  PubMed  CAS  Google Scholar 

  40. Ferri, C., Carlomagno, A., Coassin, S., Baldoncini, R., and Cassone-Faldetta, M. R. (1995). Diabetes Care 18, 226–233.

    Article  PubMed  CAS  Google Scholar 

  41. Ferri, C., Laurenti, O., Bellini, C., et al. (1995). Am. J. Hypertens. 8, 40–71.

    Article  PubMed  CAS  Google Scholar 

  42. Frank, H. J. L., Levin, E. R., Pedram, A. (1993). Endocrinology 133, 1092–1097.

    Article  PubMed  CAS  Google Scholar 

  43. Takahashi, K., Suda, K., Lam, H. C., Ghatei, M. A., and Bloom, S. R. (1991). J. Endocrinol. 130, 123–127.

    PubMed  CAS  Google Scholar 

  44. De la Rubia, G., Oliver, F. J., Inoguchi, T., and King, G. L. (1992). Diabetes 41, 1533–1539.

    Article  PubMed  Google Scholar 

  45. Bursell, S. E., Clermont, A. C., Oren, B., and King, G. L. (1995). Invest. Ophthalmol. Vis. Sci. 36, 596–607.

    PubMed  CAS  Google Scholar 

  46. Chakrabarti, S., Gan, X. T., Merry, A., Karmazyn, M., and Sima, A. A. (1998). Curr. Eye Res. 17, 301–307.

    Article  PubMed  CAS  Google Scholar 

  47. Chakrabarti, S. and Sima, A. A. (1997). Diabetes Res. Clin. Pract. 37, 109–120.

    Article  PubMed  CAS  Google Scholar 

  48. Chakrabarthy, U., Hayes, R. G., Stitt, A. W., and Douglas, A. (1997). Invest. Ophthalmol. Vis. Sci. 38, 2144–2151.

    Google Scholar 

  49. Takagi, C., Bursell, S. E., Lin, Y. W., et al. (1996). Invest. Ophthalmol. Vis. Sci. 37, 2504–2518.

    PubMed  CAS  Google Scholar 

  50. Mogensen, C. E., Østerby, R., and Gundersen, H. J. G. (1979). Diabetologia 17, 71–76.

    Article  PubMed  CAS  Google Scholar 

  51. Vora, J. P., Dolben, J., Dean J. D., et al. (1992). Kidney Int. 41, 829–835.

    Article  PubMed  CAS  Google Scholar 

  52. Lam, H. C., Lee, J. K., Chiang, H. T., et al. (1995). J. Cardiovasc. Pharmacol. 26(Suppl. 3), S479-S481.

    PubMed  CAS  Google Scholar 

  53. De-Mattia, G., Cassone-Faldetta, M., Bellini, C., et al. (1998). Am. J. Hypertens. 11, 983–988.

    Article  PubMed  CAS  Google Scholar 

  54. Shin, S. J., Lee, Y. J., Lin, S. R., Tan, M. S., Lai, Y. H., and Tsai, J. H. (1995). Nephron 70, 486–493.

    PubMed  CAS  Google Scholar 

  55. Awazu, M., Parker, R. E., Harvie, B. R., Ichikawa, I., and Kon, V. (1991). J. Cardiovasc. Pharmacol. 17(Suppl. 7), S500-S502.

    Article  PubMed  CAS  Google Scholar 

  56. Hurst, R. D., Stevanovic, Z. S., Munk, S., et al. (1995). Diabetes 44, 759–766.

    Article  PubMed  CAS  Google Scholar 

  57. Anderson, S. and Brenner, B. M. (1988). Diabetes Metab. Rev. 4, 163–177.

    Article  PubMed  CAS  Google Scholar 

  58. Lee, Y. J., Shin, S. J., and Tsai, J. H. (1994). Diabetes Care 17, 253–266.

    Google Scholar 

  59. Orisio, S., Benigni, A., Bruzzi, I., et al. (1993). Kidney Int. 43, 354–358.

    Article  PubMed  CAS  Google Scholar 

  60. Zoccali, C., Leonardis, D., Parlongo, S., Mallamaci, F., and Postorino, M. (1995). Nephrol. Dial. Transplant 10, 1320–1323.

    PubMed  CAS  Google Scholar 

  61. Simonson, M. S., Wann, S., Mene, P., et al. (1989). J. Clin. Invest. 83, 708–712.

    Article  PubMed  CAS  Google Scholar 

  62. Ishimura, E., Shouji, S., Nishizawa, Y., Morii, H., and Kashgarian, M. (1991). J. Am. Soc. Nephrol. 2, 546.

    Google Scholar 

  63. Nayer, W. G. (1990). Endothelin and the kidney. In: The Endothelins. Nayer, W. G. (ed.). Springer-Verlag: Berlin.

    Google Scholar 

  64. Dyck, P. J. (1989). Neurology 39, 111–118.

    PubMed  CAS  Google Scholar 

  65. Cameron, N. E., Cotter, M. A., and Low, P. A. (1991). Am. J. Physiol. 261, E1-E8.

    PubMed  CAS  Google Scholar 

  66. Tuck, R. R., Schmelzer, J. D., and Low, P. A. (1984). Brain 107, 935–950.

    Article  PubMed  Google Scholar 

  67. Pugliese, G., Tilton, R. G., Speedy, A., et al. (1989). Diabetologia 32, 845–857.

    Article  PubMed  CAS  Google Scholar 

  68. Zochodne, D. W. and Ho, L. T. (1992). Can. J. Physiol. Pharmacol. 70, 651–659.

    PubMed  CAS  Google Scholar 

  69. Zochodne, D. W., Ho, L. T., and Allison, J. A. (1994). J. Neurol. Sci. 127, 36–42.

    Article  PubMed  CAS  Google Scholar 

  70. Nukada, H. (1986). Diabetes 35, 1058–1061.

    Article  PubMed  CAS  Google Scholar 

  71. Nukada, H. (1992). Muscle Nerve 15, 1116–1122.

    Article  PubMed  CAS  Google Scholar 

  72. Kihara, M. and Low, P. A. (1995). Exp. Neurol. 132, 180–185.

    Article  PubMed  CAS  Google Scholar 

  73. Zochodne, D. W., Ho, L. T., and Gross, P. M. (1992). Am. J. Physiol. 263, H1806-H1810.

    PubMed  CAS  Google Scholar 

  74. Zochodne, D. W., Cheng, C. and Sun, H. (1996). Diabetes 45, 627–632.

    Article  PubMed  CAS  Google Scholar 

  75. Lam, H. C., Takahashi, K., Ghatei, M. A., Warrens, A. N., Rees, A. J., and Bloom, S. R. (1991). J. Cardiovasc. Pharmacol. 17(Suppl. 7), S390-S393.

    Article  PubMed  CAS  Google Scholar 

  76. Cameron, N. E. and Cotter, M. A. (1996). J. Pharmacol. Exp. Ther. 278, 1262–1268.

    PubMed  CAS  Google Scholar 

  77. Cameron, N. E., Dines, K. C., and Cotter, M. A. (1994). Diabetologia 37, 1209–1215.

    PubMed  CAS  Google Scholar 

  78. Bassirat, M. and Khalil, Z. (2000). Microvasc. Res. 59, 88–98.

    Article  PubMed  CAS  Google Scholar 

  79. Stevens, E. J. and Tomlinson, D. R. (1995). Br. J. Pharmacol. 115, 373–379.

    PubMed  CAS  Google Scholar 

  80. Francavilla, S., Properzi, G., Bellini, C., Marino, G., Ferri, C., and Santucci, A. (1997). J. Urol. 158, 1770–1774.

    Article  PubMed  CAS  Google Scholar 

  81. Saenz de Tejada, I., Carson, M. P., De Las Morenas, A., Goldstein, I., and Traish, A. M. (1991). Am. J. Physiol. 261, H1078-H1085.

    PubMed  CAS  Google Scholar 

  82. Takahashi, K., Ghatei, M. A., Lam, H. C., O'Halloram, D. J., and Bloom, S. R. (1990). Diabetologia 33, 306–310.

    Article  PubMed  CAS  Google Scholar 

  83. Morise, T., Takeuchi, Y., Kawano, M., Koni, I., and Takeda, R. (1995). Diabetes Care 18, 87–89.

    Article  PubMed  CAS  Google Scholar 

  84. Kawamura, M., Ohgawara, H., Naruse, M., et al. (1992). Diabetes Care 15, 1396,1397.

    Article  PubMed  CAS  Google Scholar 

  85. Donatelli, M., Colletti, I., Bucalo, M. L., Russo, V., and Verga, S. (1994) Diabetes Res. 25, 159–164.

    PubMed  CAS  Google Scholar 

  86. Letizia, C., Iannaccone, A., Cerci, S., et al. (1997). Horm. Metab. Res. 29, 247–251.

    PubMed  CAS  Google Scholar 

  87. Laurenti, O., Vingolo, E. M., Desideri, G. B., et al. (1997). Exp. Clin. Endocrinol. Diabetes 105(Suppl. 2), 40–42.

    Article  PubMed  CAS  Google Scholar 

  88. Haak, T., Jungmann, E., Felber, A., Hillmann, U., and Usadel, K. H. (1992). Am. J. Hypertens. 5, 161–166.

    PubMed  CAS  Google Scholar 

  89. Bertello, P., Veglio, F., Pinna, G., Guridi, L., Molino, P., Albano, S., and Chiandussi, L. (1994). Diabetes Care 17, 574–577.

    Article  PubMed  CAS  Google Scholar 

  90. Kamoi, K., Ishibashi, M., and Yamaji, T. (1994). Diabetes Res. Clin. Pract. 24, 125–129.

    Article  PubMed  CAS  Google Scholar 

  91. Tsunoda, K., Abe, K., Sato, T., Yokosawa, S., and Yoshinaga, K. (1991). Clin. Exp. Pharmacol. Physiol. 18, 731,732.

    PubMed  CAS  Google Scholar 

  92. Hoffman, A., Grossman, E., and Keiser, H. R. (1990) Eur. J. Pharmacol. 182, 603–606.

    Article  PubMed  CAS  Google Scholar 

  93. Teuscher, A., Schnell, H., and Wilson, P. W. F. (1988). Diabetes Care 11, 246–251.

    Article  PubMed  CAS  Google Scholar 

  94. Tolins, J. P. and Raij, L. (1989). Am. J. Med. 87 (Suppl. 6A), 29S-33S.

    Article  PubMed  CAS  Google Scholar 

  95. Kasiske, B. L., Kalil, R. S. N., Ma, J. Z., Liao, M., and Keane, W. F. (1993). Ann. Intern. Med. 118, 129–138.

    PubMed  CAS  Google Scholar 

  96. Marre, M., Chatellier, G., Leblanc, H., Guyene, T. T., Menard, J., and Passa, P. (1988). BMJ 297, 1092–1095.

    PubMed  CAS  Google Scholar 

  97. Mathiesen, E. R., Hommel, E., Giese, J., and Parving, H. H. (1991). BMJ 303, 81–87.

    Article  PubMed  CAS  Google Scholar 

  98. Chaturvedi, N., Sjolie, A. K., Stephenson, J. M., et al. (1998). Lancet 351, 28–31.

    Article  PubMed  CAS  Google Scholar 

  99. Yoshida, H. and Nakamura, M. (1992). Life Sci. 50, 195–200.

    Article  Google Scholar 

  100. Lam, H. C., Lee, J. K., Koh, S. J., and Chiang, H. T. (1996). Acute effect of captopril on urinary excretion of endothelin in normal Chinese subjects. In: Adrenal glands, vascular system and hypertension. Vinson G. P. and Anderson, D. C. (eds.). Journal of Endocrinology Ltd: Bristol, pp. 253–257.

    Google Scholar 

  101. Ferri, C., Laurenti, O., Bellini, C., et al. (1995). Am. J. Hypertens. 8, 40–47.

    Article  PubMed  CAS  Google Scholar 

  102. Lam, H. C., Lee, J. K., Chiang, H. T., Chuang, M. J., and Wang, M. C. (1998). J. Cardiovasc. Pharmacol. 31(Suppl. 1), S496-S500.

    Article  PubMed  CAS  Google Scholar 

  103. Fukui, M., Nakamura, T., Ebihara, I., et al. (1994). J. Lab. Clin. Med. 123, 763–768.

    PubMed  CAS  Google Scholar 

  104. Hocher, B., Lun, A., Priem, F., Neumayer, H. H., and Raschack, M. (1998). J. Cardiovasc. Pharmacol. 31(Suppl. 1), S492-S495.

    Article  PubMed  CAS  Google Scholar 

  105. Coutinho, M., Gerstein, H. C., Wang, Y., and Yusuf, S. (1999). Diabetes Care 22, 233–240.

    Article  PubMed  CAS  Google Scholar 

  106. Townend, J., Doran, J., Jones, S., and Davies, M. (1994). Int. J. Cardiol. 43, 299–304.

    Article  PubMed  CAS  Google Scholar 

  107. Grenier, O., Pousset, F., Isnard, R., et al. (1996). Cardiovasc. Drugs Ther. 10, 561–565.

    Article  PubMed  CAS  Google Scholar 

  108. Galatius-Jensen, S., Wroblewski, H., Emmeluth, C., Bie, P., Haunso, S., and Kastrup, J. (1996). Cardiovasc. Res. 32, 1148–1154.

    Article  PubMed  CAS  Google Scholar 

  109. Lerman, A., Hildebrand, F. L., Aarhus, L. L., and Burnett, J. C. (1991). Circulation 83, 1804–1814.

    Google Scholar 

  110. Monge, J. C. (1998). J. Cardiovasc. Pharmacol. 32(Suppl. 2), S36-S42.

    PubMed  CAS  Google Scholar 

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Lam, HC. Role of endothelin in diabetic vascular complications. Endocr 14, 277–284 (2001). https://doi.org/10.1385/ENDO:14:3:277

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