Ageing-exaggerated proliferation of vascular smooth muscle cells is related to attenuation of Jagged1 expression in endothelial cells.
OBJECTIVE
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.


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 alpha-smooth muscle actin and calponin expression and also intensified the PDGF-increased growth and migration of the co-cultured VSMC.


CONCLUSIONS
Ageing enhanced VSMC proliferation, at least in part, through impairing Jagged1 expression in the EC after vascular injury.
Wu
Xiaojing
X
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, PR China.
Zhou
Qi
Q
Huang
Lan
L
Sun
Aijun
A
Wang
Keqiang
K
Zou
Yunzeng
Y
Ge
Junbo
J
D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries; D001018:Aortic Diseases / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D006965:Hyperplasia; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072099:Serrate-Jagged Proteins; D013997:Time Factors
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D000072099:Serrate-Jagged Proteins