SIS (PLATELET-DERIVED GROWTH FACTOR-B CHAIN) GENE TRANSCRIPT LEVELS ARE ELEVATED IN HUMAN ATHEROSCLEROTIC LESIONS COMPARED TO NORMAL ARTERY
SIS (PLATELET-DERIVED GROWTH FACTOR-B CHAIN) GENE TRANSCRIPT LEVELS ARE ELEVATED IN HUMAN ATHEROSCLEROTIC LESIONS COMPARED TO NORMAL ARTERY
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DOI：
10.1073/pnas.84.4.1099
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发表时间：
1987-02-01
影响因子：
11.1
通讯作者：
BENDITT, EP
中科院分区：
文献类型：
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作者：
BARRETT, TB;BENDITT, EP
动脉平滑肌细胞（SMC）增殖被认为是人类动脉粥样硬化病变发展的一个重要方面。在这项研究中，我们提出了这样的问题：生长因子基因在动脉粥样硬化组织中是否具有转录活性？我们发现，转录的sis基因，编码血小板衍生生长因子的两条链之一，存在于手术切除的人颈动脉病变的水平5倍以上的正常动脉中检测到的组成性表达的低水平。这表明生长因子可以在人动脉粥样硬化病变内内源性合成。虽然动脉粥样硬化病变主要由SMC组成，但也可能存在大量浸润性巨噬细胞、T细胞和内皮细胞，这增加了这些次级细胞类型之一而不是SMC可能负责sis转录物的可能性。在培养物中活化的人巨噬细胞含有2- 4倍的sis RNA（每μ g总细胞RNA），而在培养物中活化的T细胞不含有显著水平的sis RNA。培养的人内皮细胞比巨噬细胞表达更高水平的sis转录本。由于培养的人动脉SMC表达受体，并对病变内细胞的sis基因的血小板衍生生长因子转录有丝分裂反应，无论这些细胞是SMC本身、巨噬细胞、内皮细胞还是其他细胞类型，都表明自分泌和/或旁分泌增殖机制在动脉粥样硬化的发病机制中很重要。
Arterial smooth muscle cell (SMC) proliferation is thought to be an essential aspect of the development of human atherosclerotic lesions. In this study we posed the question, could a growth factor gene be transcriptionally active in atherosclerotic tissue? We found that transcripts from the sis gene, which encodes one of the two chains of platelet-derived growth factor, were present in surgically removed human carotid artery lesions at levels 5-fold greater than the low level of constitutive expression detected in normal artery. This demonstrates that a growth factor could be synthesized endogenously within human atherosclerotic lesions. Although atherosclerotic lesions are composed predominantly of SMC, large numbers of infiltrating macrophages, T cells, and endothelial cells can also be present, raising the possibility that one of these secondary cell types, rather than SMC, could be responsible for the sis transcripts. Human macrophages activated in culture contained 2- to 4-fold more sis RNA, per .mu.g of total cellular RNA, than lesions, whereas T cells activated in culture did not contain significant levels. Cultured human endothelial cells expressed sis transcripts at higher levels than macrophages. Since human arterial SMC in culture express receptors for and are mitogenically responsive to platelet-derive growth factor transcription of the sis gene by cells within lesions, whether these cells are SMC themselves, macrophages, endothelial cells, or another cell type, suggests than an autocrine and/or paracrine proliferative mechanism is important in the pathogenesis of atherosclerosis.