Bone marrow-derived cells contribute to vascular inflammation but do not differentiate into smooth muscle cell lineages.

Abstract:

BACKGROUND:It has been proposed that bone marrow-derived cells infiltrate the neointima, where they differentiate into smooth muscle (SM) cells; however, technical limitations have hindered clear identification of the lineages of bone marrow-derived "SM cell-like" cells. METHODS AND RESULTS:Using a specific antibody against the definitive SM cell lineage marker SM myosin heavy chain (SM-MHC) and mouse lines in which reporter genes were driven by regulatory programs for either SM-MHC or SM α-actin, we demonstrated that although some bone marrow-derived cells express SM α-actin in the wire injury-induced neointima, those cells did not express SM-MHC, even 30 weeks after injury. Likewise, no SM-MHC(+) bone marrow-derived cells were found in vascular lesions in apolipoprotein E(-/-)mice or in a heart transplantation vasculopathy model. Instead, the majority of bone marrow-derived SM α-actin(+) cells were also CD115(+)CD11b(+)F4/80(+)Ly-6C(+), which is the surface phenotype of inflammatory monocytes. Moreover, adoptively transferred CD11b(+)Ly-6C(+) bone marrow cells expressed SM α-actin in the injured artery. Expression of inflammation-related genes was significantly higher in neointimal subregions rich in bone marrow-derived SM α-actin(+) cells than in other regions. CONCLUSIONS:It appears that bone marrow-derived SM α-actin(+) cells are of monocyte/macrophage lineage and are involved in vascular remodeling. It is very unlikely that these cells acquire the definitive SM cell lineage.

journal_name

Circulation

journal_title

Circulation

authors

Iwata H,Manabe I,Fujiu K,Yamamoto T,Takeda N,Eguchi K,Furuya A,Kuro-o M,Sata M,Nagai R

doi

10.1161/CIRCULATIONAHA.110.965202

subject

Has Abstract

pub_date

2010-11-16 00:00:00

pages

2048-57

issue

20

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.110.965202

journal_volume

122

pub_type

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