Role of bone marrow-derived cells in the genetic control of restenosis.
OBJECTIVE
Angiographic indexes of restenosis after coronary stent placement in patients show a bimodal pattern suggesting the existence of two populations with different risk of restenosis. This is reflected in the arterial remodeling response of inbred mouse strains arguing for a genetic control of the mechanisms leading to lumen narrowing. As bone marrow-derived cells (BMCs) contribute to vascular healing after arterial injury, we investigated the role of BMCs in the genetic control of restenosis.


RESULTS
129X1/SvJ mice developed significantly more neointima and late lumen loss compared to C57BL/6 mice. Gene expression analysis of intimal tissue revealed major differences in the expression of inflammatory and hematopoietic stem and progenitor cell-associated genes in response to arterial injury. In 129X1/SvJ mice stronger mobilization of lin(-)sca-1(+)CXCR4(+) cells was observed after vascular injury. Bone marrow transplantation identified the extent of neointima formation as clearly dependent on the genetic background of BMCs (ie, mice with 129X1/SvJ BMCs developed more intimal hyperplasia). The inflammatory response and the recruitment of BMCs to the site of arterial injury were significantly increased in mice with 129X1/SvJ BMCs.


CONCLUSIONS
The genetically controlled mechanisms leading to lumen narrowing in vascular remodeling are dependent on mobilization and recruitment capacities of particular BMCs.
Langwieser
Nicolas
N
Med. Klinik II-Kardiologie und Pulmologie, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Germany.
Schwarz
Johannes B K
JB
Reichenbächer
Christoph
C
Stemmer
Bastian
B
Massberg
Steffen
S
Langwieser
Nicole N
NN
Zohlnhöfer
Dietlind
D
D000818:Animals; D000950:Antigens, Ly / Q000502:physiology; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D042783:Endothelial Cells / Q000502:physiology; D005263:Femoral Artery / Q000473:pathology*; D020869:Gene Expression Profiling; D006965:Hyperplasia; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000235:genetics; D013045:Species Specificity; D017539:Tunica Intima / Q000473:pathology; D014652:Vascular Diseases / Q000235:genetics*
D000950:Antigens, Ly; C514936:CXCR4 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019718:Receptors, CXCR4