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Am J Pathol. 1993 Jun;142(6):1787-93.

Human atherosclerosis. IV. Immunocytochemical analysis of cell activation and proliferation in lesions of young adults.

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Department of Pathology, Kanazawa University, Japan.


The accumulation of smooth muscle cells is a major phenomenon associated with the pathogenesis of lesions of atherosclerosis. Smooth muscle cell proliferation in response to the release of growth factors from neighboring cells, both smooth muscle and macrophages, is one mechanism postulated to account for the increasing numbers of smooth muscle cells as atherosclerotic lesions progress. Indeed, we recently demonstrated the B chain of platelet-derived growth factor (PDGF-B), a potent smooth muscle mitogen, within macrophages in monkey and human lesions of atherosclerosis. To further test the hypothesis that smooth muscle proliferation and/or activation (eg, expression of major histocompatibility complex proteins) plays a role in the early development of these lesions, we applied antibodies to PDGF-B, HLA-DR (a marker of cell activation), and proliferating-associated marker) on a series of early human atherosclerotic lesions from young adults in conjunction with cell-type-specific antibodies. Smooth muscle cells had previously been demonstrated to comprise a major fraction of the cell population in these lesions. In a continuing study of early and intermediate lesions of individuals ranging in age from 15 to 34 years, PDGF-B was detected within macrophages in 2 of 15 lesions. There was no evidence of HLA-DR expression by the smooth muscle cell population in any of the lesions. PCNA-positive cells comprised less than 2% of the cells in the lesions, and the majority of these were blood-borne cells (macrophages and/or lymphocytes), although a small fraction of the PCNA-positive cells were identified as smooth muscle. Concurrent PCNA and 5'-bromodeoxyuridine studies of peripheral blood monocytes demonstrated the presence of significant numbers of cells positive for these proliferation-related markers. It is concluded that the growth factor PDGF-B may have a role in regulating cell proliferation in early human fatty streaks, but the number of proliferating smooth muscle cells is relatively small, and there is no evidence of smooth muscle cell activation, as judged by HLA-DR positivity, in these lesions.

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