Wu Xiaojing, Zhou Qi, Huang Lan, Sun Aijun, Wang Keqiang, Zou Yunzeng, Ge Junbo
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, PR China.
Cardiovasc Res. 2008 Mar 1;77(4):800-8. doi: 10.1093/cvr/cvm105. Epub 2007 Dec 13.
Ageing has been shown to enhance neointima formation due to abnormal growth of vascular smooth muscular cells (VSMC), which is regulated by endothelial functions. The mechanism of how endothelium affects the growth of VSMC in the process remains unclear. We here examined the role of Jagged1, a regulator of cell growth.
Male Sprague-Dawley rats at 3 (young) and 22 (old) months of age were subjected to a balloon catheter injury in the thoracic aorta. After 4 weeks, the neointima formation in the injured artery of old rats was more than that of young rats. Compared with the young rats, the increase in Jagged1 expression in the endothelium of old rats after the injury was delayed, weakened, and shortened, suggesting an impaired response of Jagged1 to the injury. In contrast, the increase in the expression of proliferating cell nuclear antigen in the neointima was more significant and maintained longer in old rats than in the young ones. Moreover, the expression of Jagged1 in the cultured arterial endothelial cells (EC) of old animals was less than those of the young ones, which promoted the Platelet-derived growth factor (PDGF)-induced growth and migration of the co-cultured VSMC. Furthermore, suppression of Jagged1 expression by a small interfering RNA in the EC of young rats reduced alpha-smooth muscle actin and calponin expression and also intensified the PDGF-increased growth and migration of the co-cultured VSMC.
Ageing enhanced VSMC proliferation, at least in part, through impairing Jagged1 expression in the EC after vascular injury.
衰老已被证明会因血管平滑肌细胞（VSMC）异常生长而增强内膜增生，这一过程受内皮功能调节。在此过程中内皮如何影响VSMC生长的机制尚不清楚。我们在此研究了细胞生长调节因子Jagged1的作用。
对3个月龄（年轻）和22个月龄（年老）的雄性Sprague-Dawley大鼠进行胸主动脉球囊导管损伤。4周后，年老大鼠损伤动脉中的内膜增生比年轻大鼠更多。与年轻大鼠相比，年老大鼠损伤后内皮中Jagged1表达的增加延迟、减弱且持续时间缩短，提示Jagged1对损伤的反应受损。相反，年老大鼠内膜中增殖细胞核抗原的表达增加比年轻大鼠更显著且持续时间更长。此外，年老动物培养的动脉内皮细胞（EC）中Jagged1的表达低于年轻动物，这促进了血小板衍生生长因子（PDGF）诱导的共培养VSMC的生长和迁移。此外，用小干扰RNA抑制年轻大鼠EC中Jagged1的表达会降低α-平滑肌肌动蛋白和钙调蛋白的表达，同时也会增强PDGF增加的共培养VSMC的生长和迁移。
衰老至少部分通过损伤血管损伤后EC中Jagged1的表达来增强VSMC增殖。
