Katsuda S, Coltrera M D, Ross R, Gown A M
Department of Pathology, Kanazawa University, Japan.
Am J Pathol. 1993 Jun;142(6):1787-93.
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.
平滑肌细胞的积聚是与动脉粥样硬化病变发病机制相关的主要现象。平滑肌细胞因邻近细胞（包括平滑肌细胞和巨噬细胞）释放生长因子而发生增殖，这是一种被认为可解释随着动脉粥样硬化病变进展平滑肌细胞数量增加的机制。事实上，我们最近在猴和人的动脉粥样硬化病变的巨噬细胞中发现了血小板源性生长因子（PDGF - B）的B链，它是一种强效的平滑肌有丝分裂原。为了进一步验证平滑肌增殖和/或激活（例如主要组织相容性复合体蛋白的表达）在这些病变早期发展中起作用的假说，我们将抗PDGF - B抗体、HLA - DR（细胞激活标志物）抗体和增殖相关标志物抗体应用于一系列来自年轻成年人的早期人类动脉粥样硬化病变，并结合细胞类型特异性抗体。此前已证明平滑肌细胞在这些病变的细胞群体中占主要部分。在一项对年龄在15至34岁个体的早期和中期病变的持续研究中，15个病变中有2个在巨噬细胞中检测到了PDGF - B。在任何病变中均未发现平滑肌细胞群体有HLA - DR表达的证据。PCNA阳性细胞占病变细胞的比例不到2%，其中大多数是血源性细胞（巨噬细胞和/或淋巴细胞），尽管一小部分PCNA阳性细胞被鉴定为平滑肌细胞。对外周血单核细胞进行的PCNA和5'-溴脱氧尿苷同步研究表明，存在大量这些与增殖相关标志物呈阳性的细胞。结论是，生长因子PDGF - B可能在调节早期人类脂肪条纹中的细胞增殖中起作用，但增殖的平滑肌细胞数量相对较少，并且根据HLA - DR阳性判断，在这些病变中没有平滑肌细胞激活的证据。
