Somatostatin receptors and the potential use of Sandostatin to interfere with vascular remodelling.
Graft vessel disease (GVD) is a major cause of graft loss after the first year following transplantation. GVD is a complex, multifunctional process that involves immunological as well as non-immunological events such as ischaemia/reperfusion injury. An important target cell to interfere with the development of GVD is the smooth muscle cell (SMC). Somatostatin (SRIF) analogues have been shown previously to inhibit the proliferation of SMC in vitro and in vivo. We provide evidence that Sandostatin, an octapeptide SRIF analogue that is known to have anti-proliferative properties on SMC proliferation, inhibits vascular remodelling in a rat angioplasty model. Furthermore, in two allotransplantation models, Sandostatin effectively interferes with the development of signs of chronic rejection/GVD. The role of the different SRIF receptor subtypes in chronic graft rejection is currently under investigation.
Bruns
C
C
Novartis Pharma AG, Preclinical Research, Basel, Switzerland. christian.bruns@pharma.novartis.com
Shi
V
V
Hoyer
D
D
Schuurman
H
H
Weckbecker
G
G
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000637:transplantation; D002455:Cell Division; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D016030:Kidney Transplantation; D051379:Mice; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000254:growth & development*; D015282:Octreotide / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism / Q000502:physiology*
D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2; D015282:Octreotide