Skip to main content
Log in

Angiogenesis: A New Factor on the Block —A Preliminary Observation

  • Published:
International Journal of Angiology

Abstract

Angiogenesis is a fundamental process which is essential to the healing of tissues including bone. Sadat–Habdan mesenchymal stimulating peptide (SHMSP) was found to enhance fracture healing. Our goal was to determine whether SHMSP has any effect on angiogenesis. A complete osteotomy of the midulna was created in 20 male, skeletally mature rabbits. In 10 rabbits at the osteotomy site 3.5 mg/kg body weight of the SHMSP was added after irrigation. The control group had only irrigation after the osteotomy was created. Postoperatively both groups received pain relief and were kept in similar circumstances. On fourth and tenth days, five rabbits from each group were sacrificed and the forelimbs were removed and sent for histopathologic examination. At four days, only the treated group showed excessive new vessel growth compared with the control groups at a ratio of 3:1 per field. The picture of neovasculization was clearer with immunochemistry staining with CD31. By the tenth day, the picture of vascularization was marginally better in the treated group and was similar to that seen on fourth day. This preliminary study shows that SHMSP has the potential for stimulating angiogenesis in a fracture module. Further studies are needed to assess its effect in other vascular insufficiencies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  1. Ausprunk DH, Folkman J (1977) Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 14:53–65

    Article  CAS  PubMed  Google Scholar 

  2. Ferrara N, (1999) Role of vascular endothelial growth factor hi regulation of angiogenesis. Kidney Int 6:794–814

    Google Scholar 

  3. Henry TD, Annex BH, McKendall GR, Azrin MA, et al. (2003) The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation 107(10):1357–1365

    Article  Google Scholar 

  4. Hershey JC, Baskin EP, Corcoran HA, Bett A, Dougherty NM, Gilberto DB, Mao X, Thomas KA, Cook JJ (2003) Vascular endothelial growth factor stimulates angiogenesis without improving collateral blood flow following hind limb ischemia in rabbits. Heart vessels 18(3):142–149

    Article  PubMed  Google Scholar 

  5. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT (1989) Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246:1309–1312

    CAS  PubMed  Google Scholar 

  6. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309

    CAS  PubMed  Google Scholar 

  7. Cavdias AX, Trueta J (1965) An experimental study of the vascular contribution to the callus of fracture. Surg Gynecol Obstet 120:731–747

    Google Scholar 

  8. Kelly PJ, Montgomery RJ, Bronk JT (1990) Reaction of the circulatory system to injury and regeneration. Clin Orthop 254:275–288

    PubMed  Google Scholar 

  9. Rhinelander FW (1968) The normal microcirculation of diaphyseal cortex and its response to fracture. J Bone Joint Surg 50A:784–800

    Google Scholar 

  10. Phillips GD, Whitehead RA, Stone AM, Ruebel MW, Goodk ML, Knighton DR (1993) Transforming growth factor β (TGF-β) stimulation of angiogenesis an electron microscopic study. J Submicrosc Cytol Pathol 25:149–155

    CAS  PubMed  Google Scholar 

  11. Wang JS (1996) Basic fibroblast growth factor for stimulation of bone formation in osteoinductive or conductive implants. Acta Orthop Scand 269(Supp1):1–33

    CAS  Google Scholar 

  12. Wang JS, Aspenberg P (1996) Basic fibroblast growth factor promotes bone ingrowth in porous hydroxyapatite. Clin Orthop 333:252–260

    PubMed  Google Scholar 

  13. Sadat-Ali M, Al Habdan I (2003) Enhancement of fracture healing by a new peptide. A preliminary report presented at European Orthopaedic Research Society, Helsinki, Finland, 156 [abstr]

    Google Scholar 

  14. Bettmann OL (ed) (1979) J Hunter: Giant of Experimental Surgery. In: A pictoral history of medicine, 5th ed. Springfield, IL: Charles C Thomas, pp 210–213

  15. Urist M (1965) Bone formation by autoinduction. Science 150:893–899

    CAS  PubMed  Google Scholar 

  16. Cook SD (1999) Preclinical and clinical evaluation of Osteogenic protein-1 (BMP-7) in bony sites. Orthopedics 22(7):669–671

    CAS  PubMed  Google Scholar 

  17. Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, et al. (2002) Recombuiant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am 84-A(12):2123–2134

    PubMed  Google Scholar 

  18. Shimmin A, Ruff S (1999) Clinical use of recombinant human osteoaenic protein-1. Bone 24: 409–431

    Google Scholar 

  19. Walker DH, Wright NM (2002) Bone morphogenetic proteins and spinal fusion. Neurosurg Focus 13(6):1–13

    CAS  Google Scholar 

  20. Heldin C-H, Miyazono K, ten Dijje P (1997) TGF-β signaling from cell membrane to nucleus via Smad proteins. Nature 390:465–471

    Article  CAS  PubMed  Google Scholar 

  21. Massague J (1998) TGF-β signal transduction. Annu Rev Biochem 67:753–791

    Article  CAS  PubMed  Google Scholar 

  22. Streeten EA, Brandi ML (1990) Biology of bone endothelial cells. Bone Miner 10:85–94

    Article  CAS  PubMed  Google Scholar 

  23. Hausman MR, Schaffler MB, Majeska RJ (2001) Prevention of fracture healing in rats by an inhibitor of angiogenesis. Bone 29(6):560–564

    Article  CAS  PubMed  Google Scholar 

  24. Beck LS, Amento EP, Xu Y, Deguzman L, Lee WP, Nguyen T, Gillett NA (1993) TGF-beta 1 induces bone closure of skull defects: temporal dynamics of bone formation in defects exposed to rh TGF-beta 1. J Bone Miner Res. 8:753–761

    CAS  PubMed  Google Scholar 

  25. Joyce ME, Jingushi S, Bolander ME (1990) Transforming growth factor-beta in the regulation of fracture repair. Orthop Clin North Am 21:199–209

    CAS  PubMed  Google Scholar 

  26. Lind M, Schumacker B, Soballe K, Keller J, Melsen F, Bunger C (1993) Transforming growth factor-beta enhances fracture healing in rabbit tibiae. Acta Ortho Scan 64:553–556

    CAS  Google Scholar 

  27. Robey PG, Young MF, Flanders KC, Roche NS, Kondaiah P, Reddi AH, Termine JD, Sporn MB, Roberts AB (1987) Osteoblasts synthesize and respond to transforming growth factor-type beta (TGF-beta) in vitro. J Cell Biol 106:457–463

    Google Scholar 

  28. Sandberg MM, Aro HT, Vuorio EI (1993) Gene expression during fracture repair. Clin Orthop 289:292–312

    PubMed  Google Scholar 

  29. Hockel M, Burke FJ (1989) Angiotropin treatment prevents flap necrosis and enhances dermal regeneration in rabbits. Arch Sura 124:693–698

    CAS  Google Scholar 

  30. Takeshita S, Zheng LP, Brogi E, Kearney M, Pu LQ, (1994) Therapeutic angiogenesis. A single intra-arterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. J Clin Invest 93:662–670

    CAS  PubMed  Google Scholar 

  31. Griffioen AW, Molema G (2000) Angiogenesis: Potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases and chronic inflammation. Pharmacol Rev 52:237–268

    CAS  PubMed  Google Scholar 

  32. Lazarous DF, Scheinowitz M, Shou M, Hodge E, Rajanayagam S, Hunsberger S, Robison WG Jr, Stiber JA, Correa R, Epstein SE, et al. (1995) Effect of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart. Circulation 91:145–153

    CAS  PubMed  Google Scholar 

  33. Unger EF, Banai S, Shou M, Lazarous DP, Jaklitsch MT, Scheinowitz M, Correa R, Klingbeilc, Epstein S (1994) Basic flbroblast growth factor enhances myocardial collateral flow in canine model. Am J Physiol 266:1588–1595

    Google Scholar 

  34. Rajanayagam MA, Shou M, Thirumurti V, Lazarous DF, Quyyumi AA, Goncalves L, Stiber J, Epstein SE, Unger EF (2000) Intracoronary basic fibroblast growth factor enhances myocardial collateral perfusions in dogs. J Am Coll Cardiol 35(2):519–526

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mir Sadat-Ali M.B.B.S., M.S., Ph.D., F.R.C.S., D.Orth., F.I.C.S..

About this article

Cite this article

Sadat-Ali, M., Al-Habdan, I. & Shawarby, M.A. Angiogenesis: A New Factor on the Block —A Preliminary Observation. Int J Angiol 14, 87–91 (2005). https://doi.org/10.1007/s00547-005-2010-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00547-005-2010-5

Keywords

Navigation