PRODUCTION OF PLATELET-DERIVED GROWTH-FACTOR LIKE MITOGEN BY SMOOTH-MUSCLE CELLS FROM HUMAN ATHEROMA
PRODUCTION OF PLATELET-DERIVED GROWTH-FACTOR LIKE MITOGEN BY SMOOTH-MUSCLE CELLS FROM HUMAN ATHEROMA
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DOI：
10.1056/nejm198806093182303
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发表时间：
1988-06-09
影响因子：
158.5
通讯作者：
BIRINYI, LK
中科院分区：
文献类型：
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作者：
LIBBY, P;WARNER, SJC;BIRINYI, LK
血管平滑肌细胞的增殖发生在动脉粥样硬化的发展和伴随慢性全身性或肺动脉高压的动脉重塑过程中。为了帮助确定启动异常生长的信号，我们培养了来自人类动脉粥样硬化斑块的平滑肌细胞。这些细胞（n = 9）向培养基中释放物质，刺激主动脉平滑肌细胞增殖至平均（±）。SD) 5.1级。为对照培养基的1倍。这种活性的部分原因是由于类似于最初从血小板中分离出来的有丝分裂原的分子，称为血小板衍生生长因子（PDGF），因为这些细胞释放PDGF，在放射性受体试验中测量（355 .+-）。每48小时117 pg /毫升；n = 6)，因为抗pdgf抗体中和了38 .+-。有丝分裂活性的7%（范围，13%至60%；n = 6个颈动脉斑块分离株）。两个平均基因编码不同的PDGF亚基，形成不同组合的二聚体，以产生具有生物活性的PDGF。从人动脉粥样硬化中培养的细胞含有PDGF A链的mrna（17株中有16株），但没有编码PDGF B链（c-sis原癌基因产物）的mrna（13株中没有）。我们得出结论，来自病变人动脉的平滑肌细胞可以分泌有丝分裂活性，其中一些类似于PDGF，这些细胞选择性地表达PDGF A链的基因。这种产生内源性的、潜在的自我刺激（自分泌）生长因子的能力可能有助于解释平滑肌细胞的复制是如何开始的，即使内皮屏障在形态上保持完整，在动脉粥样硬化的早期。
Proliferation of vascular smooth-muscle cells occurs during the development of atherosclerosis and the remodeling of arteries that accompanies chronic systemic or pulmonary hypertension. To help define the signals that initiate the abnormal growth, we cultured smooth-muscle cells from human atherosclerotic plaques. These cells (n = 9) released material into their culture medium that stimulated the proliferation of aortic smooth-muscle cells to a mean (.+-. SD) level 5.1 1 .+-. 1 times that in control medium. Part of this activity was due to molecules that resemble a mitogen first isolated from platelets and known as platelet-derived growth factor (PDGF), since these cells released PDGF measured in a radioreceptor assay (355 .+-. 117 pg per milliliter per 48 hours; n = 6) and since anti-PDGF antibody neutralized 38 .+-. 7 percent of this mitogenic activity (range, 13 to 60 percent; n = 6 carotid-plaque isolates). Two mean genes encode distinct PDGF subunits that form dimers in different combinations to create biologically active PDGF. Cells cultured from human atheroma contrained mRNAs for the PDGF A chain (16 of 17 isolates) but none (of 13) that encoded PDGF B chain (the c-sis protooncogene product). We conclude that smooth-muscle cells from diseased human arteries can secrete mitogenic activity, some of which resembles PDGF, and that these cells express the gene for the PDGF A chain selectively. This capacity to produce an endogenous, potentially self-stimulatory (autocrine) growth factor may help to explain how replication of smooth-muscle cells can begin, even while the endothelial barrier remains morphologically intact, eary in atherogenesis.