Mausmodelle zur erforschung der intimahyperplasie

TY - JOUR

T1 - Mausmodelle zur erforschung der intimahyperplasie

AU - Larena-Avellaneda, A.

AU - Winkler, M.

AU - Shimizu, T.

AU - Reidy, M. A.

AU - Daum, G.

PY - 2009/2

Y1 - 2009/2

N2 - Intimal hyperplasia (IH) is one of the major problems after vascular interventions. Despite the identification of multiple processes thought to be involved, the molecular mechanisms controlling IH are still not understood. Mouse models of arterial injury are now widely used to study IH because they allow the investigation of individual genes in knock-out animals. Moreover, it has been demonstrated that the extent of IH varies among inbred strains; thus, mouse models can be used to identify genetic loci that correlate with IH. A suitable vessel for injury experiments in mice is the carotid artery. There are different ways to induce IH in the mouse carotid: denudation of the endothelium with a catheter (nylon loop or angioplasty guide wire), complete ligation of the common carotid, dilatation by a balloon catheter, or venous grafts. In this paper, current studies in two areas of IH research are presented. First, a novel role for the bioactive lipid sphingosine-1-phosphate (S1P) is described. The hypothesis is that S1P promotes differentiation of smooth muscle cells (SMCs) by activating the type-2 receptor for S1P. Increased expression of SMC differentiation genes is thought to restrict the proliferative potential of these cells, thereby limiting IH. Second, a role for stem cells in IH is discussed. Although functional data are largely lacking, endothelial progenitor cells as well as mesenchymal stem cells have been found in murine intimal lesions. A potentially confounding aspect in IH research are observations indicating that the extent of IH after arterial injury depends not only on the nature of the injury but also on the vascular bed. In conclusion, multiple parameters define the reponse to arterial injury; therefore, the mechanisms underlying IH may be much less uniform than commonly assumed.

AB - Intimal hyperplasia (IH) is one of the major problems after vascular interventions. Despite the identification of multiple processes thought to be involved, the molecular mechanisms controlling IH are still not understood. Mouse models of arterial injury are now widely used to study IH because they allow the investigation of individual genes in knock-out animals. Moreover, it has been demonstrated that the extent of IH varies among inbred strains; thus, mouse models can be used to identify genetic loci that correlate with IH. A suitable vessel for injury experiments in mice is the carotid artery. There are different ways to induce IH in the mouse carotid: denudation of the endothelium with a catheter (nylon loop or angioplasty guide wire), complete ligation of the common carotid, dilatation by a balloon catheter, or venous grafts. In this paper, current studies in two areas of IH research are presented. First, a novel role for the bioactive lipid sphingosine-1-phosphate (S1P) is described. The hypothesis is that S1P promotes differentiation of smooth muscle cells (SMCs) by activating the type-2 receptor for S1P. Increased expression of SMC differentiation genes is thought to restrict the proliferative potential of these cells, thereby limiting IH. Second, a role for stem cells in IH is discussed. Although functional data are largely lacking, endothelial progenitor cells as well as mesenchymal stem cells have been found in murine intimal lesions. A potentially confounding aspect in IH research are observations indicating that the extent of IH after arterial injury depends not only on the nature of the injury but also on the vascular bed. In conclusion, multiple parameters define the reponse to arterial injury; therefore, the mechanisms underlying IH may be much less uniform than commonly assumed.

KW - Intimal hyperplasia

KW - Mouse model

KW - Sphingosine-1-phosphate

KW - Stem cells

KW - Vascular graft restenosis

UR - http://www.scopus.com/inward/record.url?scp=60149111144&partnerID=8YFLogxK

U2 - 10.1007/s00772-008-0649-x

DO - 10.1007/s00772-008-0649-x

M3 - SCORING: Zeitschriftenaufsatz

AN - SCOPUS:60149111144

VL - 14

SP - 9

EP - 15

JO - GEFASSCHIRURGIE

JF - GEFASSCHIRURGIE

SN - 0948-7034

IS - 1

ER -