Kaartinen M, Penttilä A, Kovanen P T
Wihuri Research Institute, Helsinki, Finland.
Atherosclerosis. 1996 Jun;123(1-2):123-31. doi: 10.1016/0021-9150(95)05794-3.
Mast cells have been assigned a role in neovascularization. Therefore, we examined the deep regions of human coronary atheromas, the areas known to be prone to neovascularization, for the presence of mast cells. Specimens of atherosclerotic human coronary intima from 37 autopsy cases with ages of 24-84 years were stained with elastica-van Gieson to detect atheroma formation and with monoclonal antibody against von Willebrand factor to detect neovascularization. Mast cells were detected by staining the atheromas with monoclonal antibodies against the two major proteases of mast cells, tryptase and chymase. Of the 24 coronary atheromas found, 13 contained mast cells in the deep regions. All these 13 deep regions also displayed neovascularization, and the number of microvessels and the number of mast cells around the microvessels correlated strongly with the size of the atheroma. On the other hand, of the 11 deep regions lacking mast cells, only one displayed neovascularization. In the neovascularized areas of the coronary atheromas, the mast cells were in close proximity to the microvessels. All the mast cells contained tryptase, and some of them chymase, both known for their angiogenic and matrix-degrading potential. In light microscopic studies, degranulated mast cells were observed indicating activation of these cells, with release of tryptase and chymase. The selective localization of activated mast cells containing angiogenic factors around newly formed microvessels in human coronary atheromas suggests that mast cells play a role in the neovascularization of these lesions. Moreover, mast cells may also, by virtue of their neutral proteases, injure the microvessels, and thereby produce intraplaque hemorrhages and, ultimately, unstable lesions.
肥大细胞在新生血管形成中发挥作用。因此,我们检查了人类冠状动脉粥样硬化斑块的深部区域(已知该区域易于发生新生血管形成),以确定是否存在肥大细胞。对37例年龄在24 - 84岁的尸检病例的动脉粥样硬化人类冠状动脉内膜标本进行弹性纤维 - 范吉森染色以检测动脉粥样硬化形成,并用抗血管性血友病因子单克隆抗体检测新生血管形成。通过用抗肥大细胞两种主要蛋白酶(类胰蛋白酶和糜酶)的单克隆抗体对动脉粥样硬化斑块进行染色来检测肥大细胞。在发现的24个冠状动脉粥样硬化斑块中,有13个在深部区域含有肥大细胞。所有这13个深部区域也都显示有新生血管形成,并且微血管数量以及微血管周围的肥大细胞数量与动脉粥样硬化斑块大小密切相关。另一方面,在11个缺乏肥大细胞的深部区域中,只有1个显示有新生血管形成。在冠状动脉粥样硬化斑块的新生血管形成区域,肥大细胞紧邻微血管。所有肥大细胞都含有类胰蛋白酶,其中一些还含有糜酶,这两种酶都以其促血管生成和基质降解潜能而闻名。在光学显微镜研究中,观察到脱颗粒的肥大细胞,表明这些细胞被激活,释放了类胰蛋白酶和糜酶。在人类冠状动脉粥样硬化斑块中,含有血管生成因子的活化肥大细胞选择性地定位于新形成的微血管周围,这表明肥大细胞在这些病变的新生血管形成中发挥作用。此外,肥大细胞还可能因其中性蛋白酶而损伤微血管,从而导致斑块内出血,并最终形成不稳定病变。