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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1551.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Role of Bone Marrow–Derived Cells in the Genetic Control of Restenosis

Nicolas Langwieser; Johannes B.K. Schwarz; Christoph Reichenbächer; Bastian Stemmer; Steffen Massberg; Nicole N. Langwieser; Dietlind Zohlnhöfer

From the Med. Klinik II-Kardiologie und Pulmologie (N.L., J.B.K.S., N.N.L., D.Z.), Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Germany; and Deutsches Herzzentrum und 1. Medizinische Klinik (C.R., B.S., S.M.), Technische Universität München, Germany.

Correspondence to Dietlind Zohlnhöfer-Momm, Med. Klinik II-Kardiologie und Pulmologie, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. E-mail dietlind.zohlnhoefer{at}charite.de

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 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.

Human restenosis shows a bimodal pattern. Similar, 129X1/SvJ mice developed more neointima formation compared to C57BL/6 mice with differences in inflammatory and hematopoietic stem cell–associated genes and stronger mobilization of lin^–sca-1⁺CXCR4⁺ cells. Bone marrow transplantation revealed stronger neointima formation, inflammatory response, and recruitment of BMCs in mice with 129X1/SvJ BMCs.

Key Words: bone marrow cells • inflammation • hematopoietic stem and progenitor cells • vascular remodeling

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Genetic Susceptibility to Restenosis: Role of Bone Marrow Cells and Inflammatory Response

Masafumi Takahashi
Arterioscler Thromb Vasc Biol 2009 29: 1407-1408. [Extract] [Full Text] [PDF]

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				M. Takahashi Genetic Susceptibility to Restenosis: Role of Bone Marrow Cells and Inflammatory Response Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1407 - 1408. [Full Text] [PDF]