Article Text

Download PDFPDF
P4 Insulin-like growth factor binding protein-2 (IGFBP-2) and its role in angiogenesis
  1. P Shah,
  2. N Haywood,
  3. P Cordell,
  4. A Bruns,
  5. H Viswambharan,
  6. K Kain,
  7. SB Wheatcroft
  1. Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, Multidisciplinary Cardiovascular Research Centre, University of Leeds, UK


Ischaemic heart disease (IHD) presents a significant burden on global morbidity, healthcare costs and patient wellbeing, therefore novel therapeutic methods for IHD are urgently needed. A family of proteins demonstrating potential in therapeutic angiogenesis is the insulin like growth factor binding proteins (IGFBPs). The family of IGFBPs (IGFBP-1-7) modulate IGF bioactivity and bioavailability. Several members of the IGFBP family exert IGF-independent cellular effects and are signalling molecules implicated in many physiological processes, including angiogenesis, which may be exploited therapeutically. IGFBP-2 possesses IGF binding domains, an Arg-Gly-Asp integrin-recognition motif and heparin-binding domains (HBDs), therefore promoting high affinity IGF binding, integrin recruitment and glycosaminoglycan interactions (via the HBD). IGFBP-2 possesses a nuclear localisation sequence, enabling its entry into the nucleus.

The effect of IGFBP-2 on angiogenic signalling pathways was investigated using Human Umbilical Vein Endothelial Cells (HUVECs). In vitro angiogenic assays were employed to study the angiogenic properties of IGFBP-2 in HUVECs.

HUVECs possessed highest endogenous expression levels of IGFBP-2 across a range of different cell types. IGFBP-2 stimulated HUVECs exhibited dose- and time-dependent enhancement in AKT activation. Maximum Akt phosphorylation was achieved with 200 ng/ml IGFBP-2. HUVECs stimulated with IGFBP-2 at different time intervals demonstrated immediate Akt activation at 15 minutes. Addition of IGFBP-2 to HUVECs significantly enhanced cell adhesion, migration and tube formation.

Future work involves investigating the mechanisms involved within the role of IGFBP-2 in angiogenesis by exploring each domain individually. In vivo studies are planned to confirm in vitro findings, supporting IGFBP-2 as a potential novel therapeutic for angiogenesis.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.