The use of autologous saphenous vein tissue is the first choice in bypass grafting. Although preferred over synthetic grafts, significant problems leading to occlusive blockage arise. Consequently over 30% of grafts require surgical revision within the first year of implantation. Autologous vein graft tissue undergoes adaptive remodelling to accommodate the change in haemodynamic environment, in effect undergoing “arterialisation”. However, typically at anastomosis, remodelling results in excessive neointimal growth characterised by the proliferation and migration of vascular smooth muscle cells to the intimal causing expansion of the intimal layer. This hyperproliferative response ultimately develops to occlude blood flow. The excessive hyperproliferation is thought to be driven by desired remodelling, iatrogenic trauma and inflammation combined with ischaemia resulting in vein graft failure and clinical complications. Hypoxia as a consequence of global ischaemia is perhaps an important factor.
Hypoxia has been shown to modulate PLC-ɣ leading to the activation of PKC dependent- cell proliferation though mitogen activated protein kinases (MAPK) signalling pathways. Additionally, hypoxia is also responsible for the pro-mitogenic HIF-1α derived signalling pathway. The exact mechanisms of these pathways which result in the modification of cellular function including proliferation and apoptosis are not yet fully understood. Thus the project aims to investigate the role of hypoxia mediated signalling in vein graft remodelling.
- CARDIAC PROCEDURES AND THERAPY
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