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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2696.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Smooth Muscle Cells in Atherosclerosis Originate From the Local Vessel Wall and Not Circulating Progenitor Cells in ApoE Knockout Mice

Jacob F. Bentzon; Charlotte Weile; Claus S. Sondergaard; Johnny Hindkjaer; Moustapha Kassem; Erling Falk

From the Departments of Cardiology (J.F.B., E.F.), Aarhus University Hospital, and Institute of Clinical Medicine, Aarhus University; the Department of Plastic Surgery (C.W.), Aarhus University Hospital; the Department of Molecular Biology and Institute of Clinical Medicine (C.S.S.), Aarhus University; the Department of Gynecology and Obstetrics (J.H.), Aarhus University Hospital; and the Department of Endocrinology (M.K.), Odense University Hospital, Denmark.

Correspondence to Jacob Bentzon, MD, Department of Cardiology, Research Unit, Aarhus University Hospital, Brendstrupgaardsvej, 8200 Aarhus N, Denmark. E-mail jben{at}ki.au.dk

Objective— Recent studies of bone marrow (BM)-transplanted apoE knockout (apoE^–/–) mice have concluded that a substantial fraction of smooth muscle cells (SMCs) in atherosclerosis arise from circulating progenitor cells of hematopoietic origin. This pathway, however, remains controversial. In the present study, we reexamined the origin of plaque SMCs in apoE^–/– mice by a series of BM transplantations and in a novel model of atherosclerosis induced in surgically transferred arterial segments.

Methods and Results— We analyzed plaques in lethally irradiated apoE^–/– mice reconstituted with sex-mismatched BM cells from eGFP⁺apoE^–/– mice, which ubiquitously express enhanced green fluorescent protein (eGFP), but did not find a single SMC of donor BM origin among 10 000 SMC profiles analyzed. We then transplanted arterial segments between eGFP⁺apoE^–/– and apoE^–/– mice (isotransplantation except for the eGFP transgene) and induced atherosclerosis focally within the graft by a recently invented collar technique. No eGFP⁺ SMCs were found in plaques that developed in apoE^–/– artery segments grafted into eGFP⁺apoE^–/– mice. Concordantly, 96% of SMCs were eGFP⁺ in plaques induced in eGFP⁺apoE^–/– artery segments grafted into apoE^–/– mice.

Conclusions— These experiments show that SMCs in atherosclerotic plaques are exclusively derived from the local vessel wall in apoE^–/– mice.

Recent studies have concluded that SMCs in atherosclerosis can originate from circulating progenitor cells. In contrast to this hypothesis, we showed by a series of bone marrow and vessel transplantations that SMCs in atherosclerotic plaques are derived entirely from the local vessel wall in apoE knockout mice

Key Words: atherosclerosis • smooth muscle cells • adult stem cells • pathology • apoE knockout mice

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