Cardiovascular Research Advance Access originally published online on December 13, 2007
Cardiovascular Research 2008 77(4):800-808; doi:10.1093/cvr/cvm105
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Ageing-exaggerated proliferation of vascular smooth muscle cells is related to attenuation of Jagged1 expression in endothelial cells
1 Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, 180 Feng Lin Road, Shanghai 200032, Peoples Republic of China
2 The Cardiovascular Center of Xinqiao Hospital, Chongqing 400037, Peoples Republic of China
* Corresponding author. Tel: +86 21 64041990; fax: +86 21 64437078. E-mail address: ge.junbo2{at}zs-hospital.sh.cn(J.G.)/ zou.yunzeng{at}zs-hospital.sh.cn(Y.Z.)
Aims: 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.
Methods and results: 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
-smooth muscle actin and calponin expression and also intensified the PDGF-increased growth and migration of the co-cultured VSMC.
Conclusion: Ageing enhanced VSMC proliferation, at least in part, through impairing Jagged1 expression in the EC after vascular injury.
KEYWORDS Ageing; Endothelial cell; Jagged1; Neointima; Smooth muscle cell
Time for primary review: 32 days