Orekhov A N, Andreeva E R, Mikhailova I A, Gordon D
Institute of Experimental Cardiology, Cardiology Research Center, Institute for Atherosclerosis Research, Ltd., Moscow, Russia.
Atherosclerosis. 1998 Jul;139(1):41-8. doi: 10.1016/s0021-9150(98)00044-6.
Local accumulation of cells (hypercellularity) in the intima of the arterial wall as a result of cell proliferation is recognized as one of the major manifestations of human atherosclerosis. In the present study we have used a monoclonal antibody against PCNA to identify the proliferative activity, in uninvolved intima of human aorta classified as diffuse intimal thickening, and in different types of atherosclerotic lesions: specifically, initial lesion, fatty streak, fibroatheroma and fibrous plaque. As compared with a diffuse intimal thickening, the cell number in the initial lesions, fatty streaks and in a fibrolipid plaque (fibroatheroma) was 1.5-3-fold higher, while the cellularity in a fibrous plaque (fibrotic lesion) was lower than in a fibroatheroma and comparable with the cell number in the initial lesions. Using monoclonal antibodies, inflammatory cells (T- and B-lymphocytes as well as monocytes-macrophages) have been revealed in the intima. However, most (84-93%) of the intimal cells were noninflammatory cells classified as resident cells possessing the antigens of smooth muscle cells and pericytes as well as a small number of cells unidentifiable with the antibodies used. The highest number of proliferating cells was found in a fibroatheroma (11-fold higher as compared with a diffuse intimal thickening). A significant, but lesser increase of PCNA-positive cells was revealed in other types of lesions, too. The proliferative 'splash' in lipid-rich lesions suggests a relationship between the lipid accumulation in atherosclerotic intima and the stimulation of proliferation. The highest proliferative index of resident cells (i.e. percentage of the PCNA-positive cells among the total number of resident cells) was revealed in fibrotic lesions. It was approximately eight-fold higher than in a diffuse intimal thickening. The proliferative index of inflammatory cells considerably exceeded that of resident cells. However, in all types of atherosclerotic lesions and in a diffuse intimal thickening it showed no significant differences and was similar to the proliferative index of inflammatory cells isolated from peripheral blood. This suggests that an increased number of resident cells in atherosclerotic lesions can be explained by stimulation of their proliferative activity, whereas an altered inflammatory cell number is rather a result of their penetration from the blood into the subendothelial intima with a constant proliferative index.
由于细胞增殖导致动脉壁内膜中细胞局部积聚（细胞增多）被认为是人类动脉粥样硬化的主要表现之一。在本研究中，我们使用了一种针对增殖细胞核抗原（PCNA）的单克隆抗体，以鉴定人类主动脉未受累内膜（分类为弥漫性内膜增厚）以及不同类型动脉粥样硬化病变中的增殖活性，具体包括：初始病变、脂纹、纤维粥样瘤和纤维斑块。与弥漫性内膜增厚相比，初始病变、脂纹和纤维脂质斑块（纤维粥样瘤）中的细胞数量高出1.5至3倍，而纤维斑块（纤维化病变）中的细胞数量低于纤维粥样瘤，与初始病变中的细胞数量相当。使用单克隆抗体在内膜中发现了炎性细胞（T淋巴细胞、B淋巴细胞以及单核细胞 - 巨噬细胞）。然而，大多数（84% - 93%）内膜细胞是非炎性细胞，分类为具有平滑肌细胞和周细胞抗原的驻留细胞，以及少量无法用所用抗体识别的细胞。在纤维粥样瘤中发现的增殖细胞数量最多（与弥漫性内膜增厚相比高出11倍）。在其他类型的病变中也发现PCNA阳性细胞有显著但较小的增加。富含脂质病变中的增殖“激增”表明动脉粥样硬化内膜中的脂质积聚与增殖刺激之间存在关联。驻留细胞的最高增殖指数（即PCNA阳性细胞在驻留细胞总数中的百分比）在纤维化病变中被发现。它比弥漫性内膜增厚高出约8倍。炎性细胞的增殖指数大大超过驻留细胞。然而，在所有类型的动脉粥样硬化病变和弥漫性内膜增厚中，它没有显著差异，并且与从外周血中分离出的炎性细胞的增殖指数相似。这表明动脉粥样硬化病变中驻留细胞数量的增加可以通过其增殖活性的刺激来解释，而炎性细胞数量的改变更多是由于它们以恒定的增殖指数从血液渗透到内皮下内膜的结果。
