Angiogenic peptides improve blood flow and promote capillary growth in a diabetic and ischaemic mouse model

Eur J Vasc Endovasc Surg. 2010 Sep;40(3):381-8. doi: 10.1016/j.ejvs.2010.02.003. Epub 2010 Mar 11.

Abstract

Objectives: It is a common clinical observation that collateral vessel development is impaired in diabetic patients with ischaemic vascular diseases. Consequently, alternative revascularisation strategies in diabetic patients are needed. This study presents the effect and mechanism of new peptide therapeutic angiogenesis in an ischaemic and diabetic mouse model.

Design: Streptozocin-injected mice that had undergone hind-limb ischaemia were treated with angiogenic peptides. Blood flow restoration was calculated by laser Doppler imager and corroborated by histological section. For the mechanism study, endothelial cells were exposed to hypoxia and high glucose concentrations to study the effect of the peptides on proliferation and anti-apoptosis.

Results: The peptides significantly restored blood perfusion 21 days after surgery in the diabetic mice (p < 0.01) by neo-vascularisation, corroborated by an increase in capillary density. In addition, the peptides induced the proliferation of hypoxic endothelial cells (p < 0.01) and protected the cells from apoptosis in high glucose cultures.

Conclusions: This is the first approach for treatment of ischaemic vascular disease with peptides in a diabetic mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Blood Glucose / metabolism
  • Capillaries / drug effects*
  • Capillaries / pathology
  • Capillaries / physiopathology
  • Cell Hypoxia
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Collateral Circulation / drug effects
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / pathology
  • Diabetic Angiopathies / physiopathology
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Hindlimb
  • Humans
  • Ischemia / drug therapy*
  • Ischemia / etiology
  • Ischemia / pathology
  • Ischemia / physiopathology
  • Laser-Doppler Flowmetry
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / blood supply*
  • Neovascularization, Physiologic / drug effects*
  • Peptides / pharmacology*
  • Regional Blood Flow / drug effects
  • Time Factors

Substances

  • Angiogenesis Inducing Agents
  • Blood Glucose
  • Peptides