AT2 receptor and vascular smooth muscle cell differentiation in vascular development

被引:73
作者
Yamada, H [1 ]
Akishita, M [1 ]
Ito, M [1 ]
Tamura, K [1 ]
Daviet, L [1 ]
Lehtonen, JYA [1 ]
Dzau, VJ [1 ]
Horiuchi, M [1 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA
关键词
angiotensin; cell differentiation; receptors; angiotensin II; muscle; smooth; vascular; human development;
D O I
10.1161/01.HYP.33.6.1414
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
The angiotensin II type 2 (AT(2)) receptor is transiently expressed at late gestation in the fetal vasculature, but its expression rapidly declines after birth. We have previously demonstrated that the expression of this receptor mediates decline in vascular DNA synthesis that occurs at this stage of vascular development. To examine further the role of the AT(2) receptor in vasculogenesis, we have focused on the effect of the AT(2) receptor on vascular smooth muscle cell (VSMC) differentiation. In this study, we examined the time-dependent expression of differentiation markers for VSMCs in the aorta of wild-type and AT(2) receptor-null mice, alpha-Smooth muscle actin was expressed at the early stage of differentiation and exhibited unchanged expression before and after the peak of AT(2) receptor expression, which was observed at embryonic day 20, neonatal day 1, and thereafter. No difference in alpha-smooth muscle actin expression was observed between the wild-type and AT(2) receptor-null mice. In contrast, the mRNA levels for calponin, expressed in the late stage of VSMC differentiation, were significantly higher in the wild-type mouse aorta as compared with the AT(2) receptor-null mice, which correlates with expression of the AT(2) receptor. Moreover, the protein levels of calponin and high-molecular-weight caldesmon (h-caldesmon) showed lower expression in the aorta of AT(2) receptor knockout mice at 2 and 4 weeks after birth. Taken together, our results suggest that the AT(2) receptor promotes vascular differentiation and contributes to vasculogenesis.
引用
收藏
页码:1414 / 1419
页数:6
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