DISTINCT PATTERNS OF EXPRESSION OF FIBROBLAST GROWTH-FACTORS AND THEIR RECEPTORS IN HUMAN ATHEROMA AND NONATHEROSCLEROTIC ARTERIES - ASSOCIATION OF ACIDIC FGF WITH PLAQUE MICROVESSELS AND MACROPHAGES
DISTINCT PATTERNS OF EXPRESSION OF FIBROBLAST GROWTH-FACTORS AND THEIR RECEPTORS IN HUMAN ATHEROMA AND NONATHEROSCLEROTIC ARTERIES - ASSOCIATION OF ACIDIC FGF WITH PLAQUE MICROVESSELS AND MACROPHAGES
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DOI：
10.1172/jci116847
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发表时间：
1993-11-01
影响因子：
15.9
通讯作者：
LIBBY, P
中科院分区：
文献类型：
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作者：
BROGI, E;WINKLES, JA;LIBBY, P
由于成纤维细胞生长因子（FGF）调节内皮细胞（EC）和平滑肌细胞（SMC）的重要功能，我们研究了FGF在人血管细胞和对照或动脉粥样硬化动脉中的表达。所有细胞和动脉均含有酸性（a）FGF和碱性（B）FGF mRNA。北方分析仅在五个对照动脉中的一个中检测到aFGF mRNA，但在所有五个测试的动脉粥样硬化中检测到aFGF mRNA，而bFGF mRNA水平在对照（n = 3）与斑块样本（n = 6）之间没有差异。免疫组化显示bFGF蛋白在对照血管（n = 10）中丰富，而在斑块（n = 14）中很少。相比之下，动脉粥样硬化（n = 14），而不是对照动脉（n = 10），始终表现出免疫反应性aFGF，特别是在新血管化和巨噬细胞丰富的斑块区域。由于巨噬细胞与aFGF共定位，我们测试了人单核细胞样THP-1细胞，并证明在PMA诱导的分化过程中aFGF mRNA的积累。我们还研究了编码FGF受体（FGFR）的mRNA的表达。所有细胞和动脉均含有FGFR-1 mRNA。只有$MC和对照血管有FGFR-2 mRNA，而EC和一些动脉含有FGFR-4 mRNA.与正常动脉相比，斑块中bFGF的相对缺乏表明这种生长因子可能不会促进晚期动脉粥样硬化中的细胞增殖。然而，由斑块巨噬细胞产生的aFGF可能在人类动脉粥样硬化形成期间刺激微血管的生长。
Because fibroblast growth factors (FGFs) modulate important functions of endothelial cells (EC) and smooth muscle cells (SMC), we studied FGF expression in human vascular cells and control or atherosclerotic arteries. All cells and arteries contained acidic (a) FGF and basic (b) FGF mRNA. Northern analysis detected aFGF mRNA only in one of five control arteries but in all five atheroma tested, while levels of bFGF mRNA did not differ among control (n = 3) vs. plaque specimens (n = 6). Immunolocalization revealed abundant bFGF protein in control vessels (n = 10), but little in plaques (n = 14). In contrast, atheroma (n = 14), but not control arteries (n = 10), consistently exhibited immunoreactive aFGF, notably in neovascularized and macrophage-rich regions of plaque. Because macrophages colocalized with aFGF, we tested human monocytoid THP-1 cells and demonstrated accumulation of aFGF mRNA during PMA-induced differentiation. We also examined the expression of mRNA encoding FGF receptors (FGFRs). All cells and arteries contained FGFR-1 mRNA. Only $MC and control vessels had FGFR-2 mRNA, while EC and some arteries contained FGFR-4 mRNA. The relative lack of bFGF in plaques vs. normal arteries suggests that this growth factor may not contribute to cell proliferation in advanced atherosclerosis. However, aFGF produced by plaque macrophages may stimulate the growth of microvessels during human atherogenesis.