Musashi-1 expression in atherosclerotic arteries and its relevance to the origin of arterial smooth muscle cells: Histopathological findings and speculations

  • Yuri V. Bobryshev
    Corresponding author at: Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia. Tel.: +61 2 9385 1217; fax: +61 2 9385 1217.
    Faculty of Medicine, University of New South Wales, Kensington, NSW 2052, Australia

    St. Vincent's Centre for Applied Medical Research and Department of Surgery, St Vincent's Hospital, University of New South Wales, Sydney, Australia
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  • Dinh Tran
    Division of Anatomical Pathology, St. Vincent's Hospital, Sydney, Australia
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  • Natalia K. Botelho
    St. Vincent's Centre for Applied Medical Research and Department of Surgery, St Vincent's Hospital, University of New South Wales, Sydney, Australia
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  • Reginald V.N. Lord
    St. Vincent's Centre for Applied Medical Research and Department of Surgery, St Vincent's Hospital, University of New South Wales, Sydney, Australia
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  • Alexander N. Orekhov
    Institute for Atherosclerosis Research, Russian Academy of Natural Sciences, Moscow, Russia

    Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia
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      The origin of smooth muscle cells in developing atherosclerotic lesions is a controversial topic with accumulating evidence indicating that at least some arterial smooth muscle cells might originate from bone marrow-derived smooth muscle cell precursors circulating in the blood. The stem cell markers currently used for the identification of stem cells in the arterial intima can be expressed by a number of different cell types residing in the arterial wall, such as mast cells, endothelial cells and dendritic cells, which can make interpretation of the data obtained somewhat ambiguous. In the present study we examined whether the putative intestinal stem cell marker Musashi-1 is expressed in the arterial wall. Using a multiplexed tandem polymerase chain reaction method (MT-PCR) and immunohistochemistry, Musashi-1 expression was revealed in human coronary arterial wall tissue segments, and this finding was followed by the demonstration of significantly higher expression levels of Musashi-1 in atherosclerotic plaques compared with those in undiseased intimal sites. Double immunohistochemistry demonstrated that in the arterial wall Musashi-1 positive cells either did not display any specific markers of cells that are known to reside in the arterial intima or Musashi-1 was co-expressed by smooth muscle α-actin positive cells. Some Musashi-1 positive cells were found along the luminal surface of arteries as well as within microvessels formed in atherosclerotic plaques by neovascularization, which supports the possibility that Musashi-1 positive cells might intrude into the arterial wall from the blood and might even represent circulating smooth muscle cell precursors.


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