Vascular Growth Factors and Atherogenesis in Diabetes Mellitus

  • T. Koschinsky
  • F. A. Gries


Severe and premature atherosclerosis often occurs in type 1 as well as in type 2 diabetic patients. The diabetes-specific reasons for this are still poorly understood [1]. Within the various pathomechanisms that are involved in the development of macrovascular disease, alterations in the growth of arterial wall cells have received increased attention, and abnormally increased growth of vacular cells is well-established as an intrinsic part of atherogenesis [2]. This paper will focus on the potential relevance of vascular growth stimulating factors that could initiate or accelerate growth of human arterial wall cells, in relation to atherogenesis in diabetes mellitus.


Growth Effect Arterial Smooth Muscle Cell Poor Metabolic Control Vascular Growth Factor Human Arterial Smooth Muscle Cell 
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  1. 1.
    Rudermann NB, Haudenschild C (1984) Diabetes as an atherogenic factor. Progr Cardiovasc Dis 26: 373–412CrossRefGoogle Scholar
  2. 2.
    Schwartz SM, Ross R (1984) Cellular proliferation in atherosclerosis and hypertension. Progr Cardiovasc Dis 26: 355–372CrossRefGoogle Scholar
  3. 3.
    Benditt EP (1977) Implications of the monoclonal character of human atherosclerotic plaques. Am J Pathol 86: 693–702PubMedGoogle Scholar
  4. 4.
    Denes R, Lehmann R, Nienhaus R (1983) Evidence of the heterogeneity of the proliferative activity in experimental diabetes. Acta Histochem 27 [Suppl]: 259–264Google Scholar
  5. 5.
    Hauss WH, Mey J, Schulte H (1979) Effect of risk factors and anti-rheumatic drugs on the proliferation of aortic wall cells. Atherosclerosis 34: 119–143PubMedCrossRefGoogle Scholar
  6. 6.
    Bowersox JC, Sorgente N (1985) Altered growth kinetics of dermal fibroblasts and arterial smooth muscle cells from spontaneously diabetic BB rats. Diabetes 34: 628–633PubMedCrossRefGoogle Scholar
  7. 7.
    Griinwald J, Hesz A, Robenek H, Briicker J, Buddecke E (1985) Proliferation, morphology, and low-density lipoprotein metabolism of arterial endothelial cells cultured from normal and diabetic minipigs. Exp Mol Pathol 42: 60–70CrossRefGoogle Scholar
  8. 8.
    Dolgov W, Zainkina OE, Bondarenko MF, Repin VS (1982) Aortic endothelium of alloxan diabetic rabbits: a quantitative study using scanning electron microscopy. Diabetologia 22: 338–343PubMedCrossRefGoogle Scholar
  9. 9.
    Ledet T, Fischer Dzoga K, Wissler RW (1976) Growth of rabbit aortic smooth-muscle cells cultured in media containing diabetic and hyperlipemic serum. Diabetes 25: 207–215PubMedCrossRefGoogle Scholar
  10. 10.
    Koschinsky T, Bunting CE, Schwippert B, Gries FA (1979) Increased growth of human fibroblasts and arterial smooth muscle cells from diabetic patients related to diabetic serum factors and cell origin. Atherosclerosis 33: 245–252PubMedCrossRefGoogle Scholar
  11. 11.
    Koh MS, Majewski BBJ, Rhodes EL (1985) Diabetic serum stimulates the proliferation of endothelial cells in culture. Diabetes Res 2: 287–289PubMedGoogle Scholar
  12. 12.
    Gerich JE (1984) Role of growth hormone in diabetes mellitus. N Engl J Med 310: 848–850PubMedCrossRefGoogle Scholar
  13. 13.
    Ledet T (1977) Growth hormone anti-serum suppresses the growth effect of diabetic serum. Diabetes 26: 798–803PubMedCrossRefGoogle Scholar
  14. 14.
    Merimee TJ, Zapf J, Froesch ER (1983) Insulin-like growth factors: studies in diabetics with and without retinopathy. N Engl J Med 309: 527–530PubMedCrossRefGoogle Scholar
  15. 15.
    Zapf J, Schoenle E, Froesch ER (1978) Insulin-like growth factors I and II: some biological actions and receptor binding characteristics of two purified constituents of non-suppressible insulin-like activity of human serum. Eur J Biochem 87: 285–296PubMedCrossRefGoogle Scholar
  16. 16.
    Stiles CD, Capone GT, Sher CD (1979) Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci USA 76: 1279–1283PubMedCrossRefGoogle Scholar
  17. 17.
    Rechler MM (1979) Receptors for somatomedins and related peptides. In: Waldhausel WK (ed) Diabetes. Excerpta Medica, Amsterdam, pp 266–271Google Scholar
  18. 18.
    King GL, Goodman AD, Buzney S, Moses A, Kahn CR (1985) Receptors and growth-promoting effects of insulin and insulin-like growth factors on cells from bovine retinal capillaries and aorta. J Clin Invest 75: 1028–1036PubMedCrossRefGoogle Scholar
  19. 19.
    King GL (1985) Cell biology as an approach to the study of the vascular complications of diabetes. Metabolism 34 [Suppl 1]: 17–34PubMedGoogle Scholar
  20. 20.
    Stout RW (1985) Overview of the association between insulin and atherosclerosis. Metabolism 34 [Suppl 1]: 7–12PubMedGoogle Scholar
  21. 21.
    Hillson RM, Hockaday TDR, Mann JI, Newton DJ (1984) Hyperinsulinemia is associated with development of electrocardiographic abnormalities in diabetics. Diabetes Res 1: 143–149PubMedGoogle Scholar
  22. 22.
    Standi E, Janka HU (1985) High serum insulin concentrations in relation to other cardiovascular risk factors in macro vascular disease of type 2 diabetes. Horm Metab Res [Suppl] 15: 46–51Google Scholar
  23. 23.
    Pfeifle B, Ditschuneit H (1981) Effect of insulin on the growth of cultured human arterial smooth muscle cells. Diabetologia 20: 155–158PubMedCrossRefGoogle Scholar
  24. 24.
    Koschinsky T, Bunting CE, Riitter R, Gries FA (1985) Sera from type 2 (non-insulin-dependent) diabetic and healthy subjects contain different amounts of a very low molecular weight growth peptide for vascular cells. Diabetologia 28: 223–228PubMedCrossRefGoogle Scholar
  25. 25.
    Taggart H, Stout RW (1980) Control of DNA synthesis in cultured vascular endothelial and smooth muscle cell. Atherosclerosis 37: 549–557PubMedCrossRefGoogle Scholar
  26. 26.
    Straus SD (1984) Growth-stimulatory actions of insulin in vitro and in vivo. Endocrinol Rev 5: 356–369CrossRefGoogle Scholar
  27. 27.
    Ross R, Vogel A (1978) The platelet-derived growth factor. Cell 14: 203–210PubMedCrossRefGoogle Scholar
  28. 28.
    Antoniades HN, Scher CD, Stiles CD (1979) Purification of human platelet-derived growth factor. Proc Natl Acad Sci USA 76: 1809–1812PubMedCrossRefGoogle Scholar
  29. 29.
    Heldin CH, Westermark B, Wasteson A (1979) Platelet-derived growth factor: purification and partial characterization. Proc Natl Acad Sci USA 76: 3722–3725PubMedCrossRefGoogle Scholar
  30. 30.
    Ross R, Bowen-Pope DF, Raines EW(1985) Platelet-derived growth factor: its potential roles in wound healing, atherosclerosis, neoplasia, and growth and development. Ciba Found Symp 116: 98–112Google Scholar
  31. 31.
    King GL, Buchwald S (1984) Characterization and partial purification of an endothelial cell growth factor from human platelets. J Clin Invest 73: 392–396PubMedCrossRefGoogle Scholar
  32. 32.
    Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn DB (1983) Transforming growth factor-ß in human platelets. J Biol Chem 258: 7155–7160PubMedGoogle Scholar
  33. 33.
    Assoian RK, Grotendorst GR, Miller DM, Sporn MB (1984) Cellular transformation by coordinated action of three peptide growth factors from human platelets. Nature 309: 804–806PubMedCrossRefGoogle Scholar
  34. 34.
    Miyazono K, Okabe T, Ishibashi S, Urabe A, Takaku F (1985) A platelet factor stimulating the proliferation of vascular endothelial cells. Exp Cell Res 159: 487–494PubMedCrossRefGoogle Scholar
  35. 35.
    Ross R (1986) Growth factors, platelets, macrophages and atherosclerosis. In: Fidge NH, Nestel PJ (eds) Atherosclerosis VII. Elsevier, Amsterdam, pp 355–358 (International congress series 696 )Google Scholar
  36. 36.
    Baird A, Esch F, Mormede P, Ueno N, Ling N, Böhlen P, Jing S-J, Wehrenberg WB, Guillemin R (1986) Molecular characterization of fibroblast growth factor: distribution and biological activities in various tissues. Hor Res 42: 143–205Google Scholar
  37. 37.
    Oka Y, Orth N (1983) Human plasma epidermal growth factor/ß-urogastrone is associated with blood platelets. J Clin Invest 72: 249–259PubMedCrossRefGoogle Scholar
  38. 38.
    Clemmons DR, William LI, Brown MT (1983) Dialyzable factor in human serum of platelet origin stimulates endothelial cell replication and growth. Proc Natl Acad Sci USA 80: 1641–1645PubMedCrossRefGoogle Scholar
  39. 39.
    Koschinsky T, Bünting CE, Schwippert B, Gries FA (1980) Increased growth stimulation of fibroblasts from diabetics by diabetic serum factors of low molecular weight. Atherosclerosis 37: 311–317PubMedCrossRefGoogle Scholar
  40. 40.
    Koschinsky T, Bünting CE, Schwippert B, Gries FA (1981) Regulation of diabetic serum growth factors for human vascular cells by the metabolic control of diabetes mellitus. Atherosclerosis 39: 313–319PubMedCrossRefGoogle Scholar
  41. 41.
    Koschinsky T, Bünting CE, Rütter R, Gries FA (1983) Diabetic growth peptides of very low molecular weight for human vascular cells in serum from type 2 (non insulin-dependent) diabetic patients. Diabetologia 25: 172–173Google Scholar
  42. 42.
    Koschinsky T, Bünting CE, Rütter R, Schütze R, Gries FA (1985) Diabetic serum growth factor: a new low molecular weight growth peptide for arterial smooth muscle cells of platelet origin. Monogr Atheroscler 13: 159–163PubMedGoogle Scholar
  43. 43.
    Born MN (1978) Platelet function in diabetes mellitus. Diabetes 27: 342–350Google Scholar
  44. 44.
    Colwell JA, Lopes-Virella M, Halushka PV (1981) Pathogenesis of atherosclerosis in diabetes. Diabetes Care 4: 121–133PubMedCrossRefGoogle Scholar
  45. 45.
    Hamet P, Sugimoto H, Umeda F, Lecavalier L, Franks DJ, Orth DN, Chiasson J-L (1985) Abnormalities of platelet-derived growth factors in insulin-dependent diabetes. Metabolism 34 [Suppl 1]: 25–31PubMedCrossRefGoogle Scholar
  46. 46.
    Bowen-Pope DF, Ross R, Seifert R (1985) Locally acting growth factors for vascular cells. Circulation 72: 735–740PubMedCrossRefGoogle Scholar
  47. 47.
    DiCorleto PE, Gajdusek CM, Schwartz SM, Ross R (1983) Biochemical properties of the endothelium-derived growth factor: comparison to other growth factors. J Cell Physiol 114: 339–345PubMedCrossRefGoogle Scholar
  48. 48.
    Gajdusek CM (1984) Release of endothelial cell-derived growth factor (ECDGF) by heparin. J Cell Physiol 121: 13–21PubMedCrossRefGoogle Scholar
  49. 49.
    Campbell JH, Campbell GR (1986) Endothelial cell influences on vascular smooth muscle phenotype. Annu Rev Physiol 48: 295–306PubMedCrossRefGoogle Scholar
  50. 50.
    Stavenow L, Tejler L (1985) Growth stimulating activity from lysed cultured arterial smooth muscle cells and skin fibroblasts. Med Biol 63: 175–181PubMedGoogle Scholar
  51. 51.
    Clemmons DR (1985) Variables controlling the secretion of a somatomedin-like peptide by cultured porcine smooth muscle cells. Circ Res 56: 418–426PubMedGoogle Scholar
  52. 52.
    Clemmons DR, Van Wyk JJ (1985) Evidence for a functional role of endogenously produced somatomedinlike peptides in the regulation of DNA synthesis in cultured human fibroblasts and porcine smooth muscle cells. J Clin Invest 75: 1914–1918PubMedCrossRefGoogle Scholar
  53. 53.
    Millis AJT, Hoyle M, Field B (1977) Human fibroblast conditioned media contains growth-promoting activities for low density cells. J Cell Physiol 93: 17–24PubMedCrossRefGoogle Scholar
  54. 54.
    Satoh T, Kan M, Kato M, Yamane I (1986) Purification and characterization of an endothelial cell growth factor from serum-free culture medium of human diploid fibroblast cells. Biochim Biophys Acta 887: 86–93PubMedCrossRefGoogle Scholar
  55. 55.
    Martin BM, Gimbrone MA, Unanue ER, Cotran RS (1981) Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor. J Immunol 126: 1510–1515PubMedGoogle Scholar
  56. 56.
    Glenn KC, Ross R (1981) Human monocyte-derived growth factor(s) for mesenchymal cells: activation of secretion by endotoxin and concanavalin A. Cell 25: 603–615PubMedCrossRefGoogle Scholar
  57. 57.
    Libby P, Wyler DJ, Janicka MW, Dinarello CA (1985) Differential effects of human interleukin–1 on growth of human fibroblasts and vascular smooth muscle cells. Arteriosclerosis 5: 186–191PubMedCrossRefGoogle Scholar
  58. 58.
    Martinet Y, Bitterman PB, Mornex JF, Grotendorst GR, Martin GR, Crystal RG (1986) Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity. Nature 319: 158–160PubMedCrossRefGoogle Scholar
  59. 59.
    Kitahara M, Eyre HJ, Lynch RE, Rallison ML, Hill HR (1980) Metabolic activity of diabetic monocytes. Diabetes 29: 251–256PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • T. Koschinsky
  • F. A. Gries

There are no affiliations available

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