Mast cells in neovascularized human coronary plaques store and secrete basic fibroblast growth factor, a potent angiogenic mediator
Mast cells in neovascularized human coronary plaques store and secrete basic fibroblast growth factor, a potent angiogenic mediator
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DOI：
10.1161/01.atv.0000140820.51174.8d
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发表时间：
2004-10-01
影响因子：
8.7
通讯作者：
Kovanen, PT
中科院分区：
文献类型：
--
作者：
Lappalainen, H;Laine, P;Kovanen, PT
目的-斑块内新生血管和出血可能促进斑块进展。我们研究了碱性成纤维细胞生长因子（bFGF），一种有效的血管生成介质，在人类冠状动脉粥样硬化程度增加的斑块中，肥大细胞（MCs）表达。方法与结果-采集30例尸检对象的正常和动脉粥样硬化冠状动脉段。采用免疫组织化学方法检测MCs、bFGF和微血管。上皮细胞和内膜细胞均可见bFGF的胞浆内颗粒染色，上皮细胞附近可见bFGF阳性的胞外颗粒。斑块新生血管区bfgf阳性MCs数量增加，内膜和外膜中bfgf阳性MCs数量与微血管数量呈正相关。在斑块中，与邻近的非血管化区相比，高度新生血管化区含有更多的bfgf阳性MCs，而非血管化区只有少量MCs存在。重要的是，表达bFGF的内膜MCs比例随着动脉粥样硬化严重程度的增加而增加。结论：目前的研究揭示了人类冠状动脉、内膜和外内膜MCs中bFGF的新来源。bFGF阳性MCs与微血管和动脉粥样硬化严重程度的关联表明，冠状动脉MCs通过释放bFGF，可能在血管生成和冠状动脉斑块进展中发挥作用。
Objective - Intraplaque neovascularization and hemorrhage may facilitate plaque progression. We studied expression of basic fibroblast growth factor ( bFGF), a potent angiogenic mediator, by mast cells (MCs) in human coronary plaques with increasing degrees of atherosclerosis.Methods and Results - Normal and atherosclerotic coronary segments were collected from 30 autopsied subjects. Immunohistochemical methods were used to detect MCs, bFGF, and microvessels. Both adventitial and intimal MCs showed intracytoplasmic granular staining for bFGF, and bFGF-positive extracellular granules were observed close to the MCs. Increased numbers of bFGF-positive MCs were detected in neovascularized areas of plaques, and there was a positive correlation between numbers of bFGF-positive MCs and microvessels in both the intima and adventitia. In plaques, the highly neovascularized areas contained increased numbers of bFGF-positive MCs compared with the adjacent nonvascularized areas, where only few MCs were present. Importantly, the proportion of intimal MCs expressing bFGF increased with increasing severity of atherosclerosis.Conclusions - The present work reveals a novel source of bFGF in human coronary arteries, the intimal and adventitial MCs. The association of bFGF-positive MCs with microvessels and with the severity of atherosclerosis suggests that coronary MCs, by releasing bFGF, may play a role in angiogenesis and progression of coronary plaques.