Hoshiga M, Alpers C E, Smith L L, Giachelli C M, Schwartz S M
Department of Pathology, University of Washington, Seattle 98195, USA.
Circ Res. 1995 Dec;77(6):1129-35. doi: 10.1161/01.res.77.6.1129.
Recent evidence suggests that alpha v beta 3 integrin is a critical molecule in several processes involved in atherosclerosis progression and in restenosis, eg, smooth muscle cell (SMC) migration and angiogenesis. While several ligands for this integrin are known to be present in atherosclerotic plaque, little is known about the presence of alpha v beta 3 integrin at this site. In the present study, we have examined alpha v beta 3 expression in normal and atherosclerotic arteries. Thirty-six coronary artery segments from the recipient hearts of 24 patients undergoing heart transplantation were classified into two groups: nonatherosclerotic diffuse intimal thickening (DIT) and atherosclerotic plaques. Serial frozen sections were examined immunohistochemically with four different monoclonal antibodies directed against human alpha v beta 3 complex or the beta 3 subunit and with cell markers for SMCs, macrophages, and endothelial cells. The endothelium along the lumen of both DIT and plaque arteries showed high expression of alpha v beta 3. The media of both DIT and plaque arteries showed less intense but extensive expression of alpha v beta 3. Immunoprecipitation and reverse-transcribed polymerase chain reaction (RT-PCR) analyses performed on extracts from the aortic media confirmed the presence of alpha v beta 3 in the media. In the intima of both DIT and plaque arteries, alpha v beta 3 expression generally colocalized with SMCs but rarely with macrophages. The microvessels in the adventitia as well as in the plaque showed prominent expression of alpha v beta 3, in contrast to low expression in similar-sized microvessels of the skin.(ABSTRACT TRUNCATED AT 250 WORDS)
近期证据表明,αvβ3整合素是动脉粥样硬化进展和再狭窄所涉及的多个过程中的关键分子,例如平滑肌细胞(SMC)迁移和血管生成。虽然已知该整合素的几种配体存在于动脉粥样硬化斑块中,但对于该部位αvβ3整合素的存在情况却知之甚少。在本研究中,我们检测了正常和动脉粥样硬化动脉中αvβ3的表达。对24例接受心脏移植患者的受体心脏的36个冠状动脉节段进行分组:非动脉粥样硬化性弥漫性内膜增厚(DIT)和动脉粥样硬化斑块。使用四种针对人αvβ3复合物或β3亚基的不同单克隆抗体以及SMC、巨噬细胞和内皮细胞的细胞标志物,对连续冰冻切片进行免疫组织化学检查。DIT和斑块动脉管腔的内皮均显示αvβ3高表达。DIT和斑块动脉的中膜均显示αvβ3表达强度较低但广泛。对主动脉中膜提取物进行的免疫沉淀和逆转录聚合酶链反应(RT-PCR)分析证实中膜存在αvβ3。在DIT和斑块动脉的内膜中,αvβ3表达通常与SMC共定位,但很少与巨噬细胞共定位。与皮肤中大小相似的微血管低表达形成对比的是,外膜以及斑块中的微血管显示αvβ3显著表达。(摘要截于250字)