Regulation of macrophage foam cell formation and atherosclerotic diseases by cell adhesion signalling

我们创建了缺乏Hic-5（一种细胞粘附分子）和apoE的双KO小鼠。血管紧张素II诱导的腹主动脉瘤发生在87%的apoE-KO小鼠中，但仅发生在11%的双KO小鼠中。从血管平滑肌细胞中特异性缺乏Hic-5的小鼠中获得了类似的结果。双KO小鼠的动脉粥样硬化病变面积被抑制至apoE-KO小鼠的40%。双基因敲除小鼠内皮细胞表面微绒毛样结构的形成受到抑制。此外，与apoE-KO小鼠相比，来自双KO小鼠的单核细胞与内皮细胞的粘附被抑制。提示血管平滑肌细胞和内皮细胞中的Hic-5在动脉粥样硬化性心血管疾病的发生发展中起重要作用。

We created double-KO mice lacking both Hic-5, a cell adhesion molecule, and apoE. Angiotensin II-induced abdominal aortic aneurysm occurred to 87% of apoE-KO mice but only to 11% of double-KO mice. Similar results were obtained from mice lacking Hic-5 specifically in vascular smooth muscle cells. Atherosclerotic lesion areas in double-KO mice were suppressed to 40% of apoE-KO mice. Formation of microvilli-like structures on endothelial cell surface was suppressed in double-KO mice. Furthermore, monocyte adhesion to endothelial cells from double-KO mice was suppressed compared with apoE-KO mice. These results suggest that Hic-5 in vascular smooth muscle cells and endothelial cells plays essential roles in the development of atherosclerotic cardiovascular diseases.