Skip to main content
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1995;8(2):103–110. doi: 10.1007/BF00344419

Effects of angiopeptin on transplant arteriosclerosis in the rat

M L Akyürek 1,, A Wanders 2, M Aurivillius 3, E Larsson 1, K Funa 3, B C Fellström 2
PMCID: PMC7087531  PMID: 7766291

Abstract

The influence of the somatostatin analogue angiopeptin on transplant arteriosclerosis was investigated using two aortic transplantation rat models. One was characterized by ischemia/reperfusion-induced changes in syngeneic transplants while immunologically induced changes dominated in the other allogeneic model. Angiopeptin, 100 μg/kg per day, was administered continuously until the sacrifice of the rats after 8 weeks. No additional immunosuppression was used in either model. An image analysis system was used to quantify the intimal and medial thicknesses of the grafts. In the syngeneic grafts, the intimal thickness was less than 50% of that of control grafts (P<0.05), but no difference was seen in the allogeneic model. The expression of selected cells, TGF-βs and PDGF and PDGF α-receptors was detected immunohistochemically and displayed a similar picture in control and angiopeptin-treated grafts in both models. We conclude that angiopeptin has no clear immunosuppressive properties but may counteract ischemia-induced transplant arteriosclerosis.

Key words: Arteriosclerosis, angiopeptin, rat; Angiopeptin, arteriosclerosis, rat; Aorta transplantation, arteriosclerosis

Footnotes

Part of this paper has previously been published in Transplant Proceedings (1993; 21: 2098–2099).

References

  • 1.Agro A, Padol I, Stanisz AM. Immunomodulatory activities of the somatostatin analogue BIM 23014c: effects on murine lymphocyte proliferation and natural killer activity. Regul Pept. 1991;32:129–132. doi: 10.1016/0167-0115(91)90041-e. [DOI] [PubMed] [Google Scholar]
  • 2.Asotra S, Foegh M, Conte JV, Cai BR, Ramwell PW. Inhibition of 3H-thymidine incorporation by angiopeptin in the aorta of rabbits after balloon angioplasty. Transplant Proc. 1989;21:3695–3696. [PubMed] [Google Scholar]
  • 3.Bhathena SJ, Recant L. Somatostatin receptors on circulating human blood cells. Horm Metab Res. 1980;12:277–278. doi: 10.1055/s-2007-996267. [DOI] [PubMed] [Google Scholar]
  • 4.Bodgen AE, Taylor JE, Moreau JP, Coy DH. Treatment of R-3327 prostate tumours with a somatostatin analogue (somatuline) as adjuvant therapy following surgical castration. Cancer Res. 1990;50:2646–2650. [PubMed] [Google Scholar]
  • 5.Bonventre JV, Weinberg JM. Kidney preservation ex vivo for transplantation. Annu Rev Med. 1992;43:523–553. doi: 10.1146/annurev.me.43.020192.002515. [DOI] [PubMed] [Google Scholar]
  • 6.Cathapermal SS, Foegh ML, Rau CS, Ramwell PW. Disposition and tissue distribution of angiopeptin in the rat. Drug Metab Dispos. 1991;19:735–739. [PubMed] [Google Scholar]
  • 7.Conte JV, Foegh M, Calcagno D, Wallace RB, Ramwell PW. Peptide inhibition of myointimal proliferation following angioplasty in rabbits. Transplant Proc. 1989;21:3686–3688. [PubMed] [Google Scholar]
  • 8.Eriksson A, Rorsman C, Ernlung A, Claesson-Welsh L, Heldin CH. Ligand induced homo- and heterodimerization of platelet-derived growth factor α- and β-receptors in intact cells. Growth Factors. 1992;6:1–14. doi: 10.3109/08977199209008867. [DOI] [PubMed] [Google Scholar]
  • 9.Fellström B, Dimény E, Larsson E, Klareskog L, Tufveson G, Rubin K. Importance of PDGF receptor expression in accelerated atherosclerosis-chronic rejection. Transplant Proc. 1989;4:3689–3691. [PubMed] [Google Scholar]
  • 10.Fellström B, Dimény E, Foegh ML, Larsson E, Wanders A, Tufeson G. Accelerated atherosclerosis in heart transplants in the rat simulating chronic vascular rejection: effects of prostacyclin and angiopeptin. Transplant Proc. 1991;23:525–528. [PubMed] [Google Scholar]
  • 11.Foegh ML. Angiopeptin: a treatment for accelerated myointimal hyperplasia? J Heart Lung Transplant. 1992;11:28–31. [PubMed] [Google Scholar]
  • 12.Foegh ML, Khirabadi BS, Chambers E, Amamoo S, Ramwell PW. Inhibition of coronary artery transplant arterioslcerosis in rabbits with angiopeptin, an octapeptide. Atherosclerosis. 1989;78:229–236. doi: 10.1016/0021-9150(89)90228-1. [DOI] [PubMed] [Google Scholar]
  • 13.Foegh ML, Khirabadi BS, Chambers E, Ramwell PW. Peptide inhibition of accelerated transplant atherosclerosis. Transplant Proc. 1989;21:3674–3676. [PubMed] [Google Scholar]
  • 14.Jacobsson J, Wahlberg J, Frödin L, Odlind B, Tufveson G. Organ flush out solutions and cold storage preservation solutions: effect on organ cooling and post ischemic erythrocyte trapping in kidney grafts. Scand J Urol Nephrol. 1989;32:219–222. doi: 10.3109/00365598909180845. [DOI] [PubMed] [Google Scholar]
  • 15.Juhlin C, Holmdahl R, Johansson H, Rastad J, Åkerström G, Klareskog L. Monoclonal antibodies with exclusive reactivity against parathyroid cells and tubule cells of the kidney. Proc Natl Acad Sci USA. 1987;84:2990–2997. doi: 10.1073/pnas.84.9.2990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Kendall TJ, Wilson JE, Radio SJ, Kandolf R, Gulizia JM, Winters GL, Costanzo-Nordin MR, Malcom GT, Thieszen SL, Miller LW, McManus BM. Cytomegalovirus and other herpes viruses: do they have a role in the development of accelerated coronary arterial disease in human heart allografts? J Heart Lung Transplant. 1992;11:14–20. [PubMed] [Google Scholar]
  • 17.Lundergan C, Foegh ML, Vargas R, Eufemio M, Bormes GW, Kot PA, Ramwell PW. Inhibition of myointimal proliferation of the rat carotid artery by peptides, angiopeptin and BIM 23034. Atherosclerosis. 1989;80:49–55. doi: 10.1016/0021-9150(89)90067-1. [DOI] [PubMed] [Google Scholar]
  • 18.Masetti P, DiSesa VJ, Schoen FJ, Sun SC, Byrne JG, Appleyard RF, Laurence R, Cohn LH. Ischemic injury before heart transplantation does not cause coronary arteriopathy in experimental isograft. J Heart Lung Transplant. 1991;10:597–599. [PubMed] [Google Scholar]
  • 19.McMaster R, Williams AF. Identification of Ia glycoprotein in the rat thymus and purification from rat spleen. Eur J Immunol. 1979;9:426–433. doi: 10.1002/eji.1830090603. [DOI] [PubMed] [Google Scholar]
  • 20.Mennander A, Tiisala S, Halttunen J, Yilmaz S, Paavonen T, Häyry P. Chronic rejection in rat aortic allografts. An experimental model for transplant arteriosclerosis. Arterioscler Thromb. 1991;11:671–680. doi: 10.1161/01.atv.11.3.671. [DOI] [PubMed] [Google Scholar]
  • 21.Mennander A, Paavonen T, Häyry P. Intimal thickening and medial necrosis in allograft arteriosclerosis (chronic rejection) are independently regulated. Arterioscler Thromb. 1993;13:1019–1025. doi: 10.1161/01.atv.13.7.1019. [DOI] [PubMed] [Google Scholar]
  • 22.Mennander A, Räisänen A, Paavonen T, Häyry P. Chronic rejection in the rat aortic allograft. V. Mechanism of the angiopeptin (BIM 23014C) effect on the generation of allograft arteriosclerosis. Transplantation. 1993;55:124–128. doi: 10.1097/00007890-199301000-00023. [DOI] [PubMed] [Google Scholar]
  • 23.Olofsson A, Miyazono K, Kanzaki T, Colosetti P, Engström U, Heldin CH. Transforming growth factor -β1, -β2, -β3 secreted by a human glioblastoma cell line. J Biol Chem. 1992;267:19482–19488. [PubMed] [Google Scholar]
  • 24.Parmar H, Charlton CD, Philips RH, Edwards L, Bejot JL, Thomas F, Lightman SL. Therapeutic response to somatostatin analogue, BIM 23014, in metastatic prostatic cancer. Clin Exp Metastasis. 1992;10:3–11. doi: 10.1007/BF00163570. [DOI] [PubMed] [Google Scholar]
  • 25.Paul LC, Fellström B. Chronic vascular rejection of the heart and the kidney-have rational treatment options emerged? Transplantation. 1992;53:1169–1179. doi: 10.1097/00007890-199206000-00001. [DOI] [PubMed] [Google Scholar]
  • 26.Payan DG, Hess CA, Goetzl EJ. Inhibition by somatostatin of the proliferation of T-lymphocytes and molt-4 lymphoblasts. Cell Immunol. 1984;84:433–438. doi: 10.1016/0008-8749(84)90117-5. [DOI] [PubMed] [Google Scholar]
  • 27.Prevost G, Lanson M, Thomas F, Veber N, Gonzalez W, Beaupain R, Starzec A, Bogden A. molecular heterogeneity of somatostatin analogue BIM-23014C receptors in human breast carcinoma cells using the chemical cross-linking assay. Cancer Res. 1992;52:843–850. [PubMed] [Google Scholar]
  • 28.Rubin K, Hansson GK, Römmstrand L, Cleasson-Welsh L, Fellström B, Tingström A, Larsson E, Klareskog L, Heldin CH, Terracio L. Induction of platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet. 1988;I:1353–1356. doi: 10.1016/s0140-6736(88)92177-0. [DOI] [PubMed] [Google Scholar]
  • 29.Russell R. The pathogenesis of atherosclerosis: a perspective for 1990s. Nature. 1993;362:801–809. doi: 10.1038/362801a0. [DOI] [PubMed] [Google Scholar]
  • 30.Sakuda H, Nakashima Y, Kuriyama S, Sueishi K. Media continued by smooth muscle cells cultured in a variety of hypoxic environments stimulates in vitro angiogenesis. A relationship to transforming growth factor-β1. Am J Pathol. 1992;141:1507–1516. [PMC free article] [PubMed] [Google Scholar]
  • 31.Scicchitano R, Stanisz AM, Payan DG, Kiyono H, McGee JR, Bienestock J. Expression of substance P and somatostatin receptors on a T helper cell line. Adv Exp Med Biol. 1987;216A:185–190. doi: 10.1007/978-1-4684-5344-7_21. [DOI] [PubMed] [Google Scholar]
  • 32.Shiraishi T, Morimoto S, Ikoh K, Sato H, Sugihara K, Onisi T, Ogihara T. Radioimmunoassay of human platelet-derived growth factor using monoclonal antibody towards a synthetic 73–79 fragment of its B-chain. Clin Chim Acta. 1989;184:65–74. doi: 10.1016/0009-8981(89)90257-x. [DOI] [PubMed] [Google Scholar]
  • 33.Stiko-Rahm A, Hultgård-Nilsson A, Regnström J, Hamsten A, Nilsson J. Oxidised and native LDL enhances production of PDGF-AA and the surface expression of PDGF receptors in cultured human arterial smooth muscle cells. Arterioscler Thromb. 1992;12:1099–1109. doi: 10.1161/01.atv.12.9.1099. [DOI] [PubMed] [Google Scholar]
  • 34.Taylor JE, Bodgen AE, Moreau JP, Coy DH. In vitro and in vivo inhibition of human small cell lung carcinoma (NCI-H69) growth by a somatostatin analogue. Biochem Biophys Res Commun. 1988;153:81–86. doi: 10.1016/s0006-291x(88)81192-6. [DOI] [PubMed] [Google Scholar]
  • 35.Taylor JE, Moreau JP, Baptiste L, Moody TW. Octapeptide analogues of somatostatin inhibit the clonal growth and vasoactive intestinal peptide-stimulated cyclic AMP formation in human small cell lung cancer cells. Peptides. 1991;12:839–843. doi: 10.1016/0196-9781(91)90143-d. [DOI] [PubMed] [Google Scholar]
  • 36.Vargas R, Bormes GW, Wroblewska B, Foegh ML, Kot PA, Ramwell PW. Angiopeptin inhibits thymidine incorporation in rat carotid artery in vivo. Transplant Proc. 1989;21:3702–3704. [PubMed] [Google Scholar]
  • 37.Waltenberger J, Wanders A, Fellström B, Miyazono K, Heldin CH, Funa K. Induction of transforming growth factor-β during cardiac allograft rejection. J Immunol. 1993;151:1147–1157. [PubMed] [Google Scholar]
  • 38.Wanders A, Akyürek ML, Waltenberger J, Stafberg C, Larsson E, Zhiping R, Funa K, Fellström B. The impact of ischemia time on chronic vascular rejection in the rat — effects of angiopeptin. Transplant Proc. 1993;21:2098–2099. [PubMed] [Google Scholar]
  • 39.Williams AF. Analysis of cell surfaces by xenogeneic mylemo-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell. 1977;12:663–673. doi: 10.1016/0092-8674(77)90266-5. [DOI] [PubMed] [Google Scholar]
  • 40.Yilmaz S, Paavonen T, Häyry P. Chronic rejection of rat renal allografts. Transplantation. 1992;53:823–827. doi: 10.1097/00007890-199204000-00023. [DOI] [PubMed] [Google Scholar]

Articles from Transplant International are provided here courtesy of Nature Publishing Group

RESOURCES