Hypoxia mediated signalling in vein graft remodelling and failure

Research output: Contribution to journalMeeting abstract

Abstract

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.

Fingerprint

Veins
Transplants
Tunica Intima
Ischemia
Saphenous Vein
Mitogen-Activated Protein Kinases
Vascular Smooth Muscle
Reoperation
Smooth Muscle Myocytes
Hemodynamics
Cell Proliferation
Hypoxia
Apoptosis
Inflammation
Wounds and Injuries
Growth

Keywords

  • bypass surgery
  • grafts
  • hypoxia

Cite this

@article{72b23f3e137d4dc7abea10460818b7c2,
title = "Hypoxia mediated signalling in vein graft remodelling and failure",
abstract = "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.",
keywords = "bypass surgery, grafts, hypoxia",
author = "M Huq and S Currie and P Coats",
year = "2014",
month = "12",
day = "31",
doi = "10.1136/heartjnl-2014-306916.16",
language = "English",
volume = "100",
journal = "Heart",
issn = "1355-6037",
number = "S4",

}

Hypoxia mediated signalling in vein graft remodelling and failure. / Huq, M; Currie, S; Coats, P.

In: Heart , Vol. 100, No. S4, 31.12.2014.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Hypoxia mediated signalling in vein graft remodelling and failure

AU - Huq, M

AU - Currie, S

AU - Coats, P

PY - 2014/12/31

Y1 - 2014/12/31

N2 - 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.

AB - 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.

KW - bypass surgery

KW - grafts

KW - hypoxia

UR - http://heart.bmj.com/

U2 - 10.1136/heartjnl-2014-306916.16

DO - 10.1136/heartjnl-2014-306916.16

M3 - Meeting abstract

VL - 100

JO - Heart

T2 - Heart

JF - Heart

SN - 1355-6037

IS - S4

ER -