Role of bone marrow-derived cells in the genetic control of restenosis

Abstract

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. METHODS AND 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 linsca-1CXCR4 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. © 2009 American Heart Association, Inc.