Vascular injury causes neointimal formation in angiotensin II type 1a receptor knockout mice.
Vascular injury causes neointimal formation in angiotensin II type 1a receptor knockout mice.
复制标题
血管紧张素 II 1a 型受体敲除小鼠的血管损伤导致新生内膜形成。
作者：
K. Harada;I. Komuro;T. Sugaya;K. Murakami;Y. Yazaki
许多使用小动物模型的研究表明，血管紧张素 II (Ang II) 在血管损伤后的新内膜形成中发挥重要作用。在本研究中，我们使用 AT1a 敲除 (KO) 小鼠检查了 Ang II 1 型受体 (AT1) 介导的 Ang II 信号传导对于损伤诱导的新内膜形成的发展是否是不可或缺的。逆转录聚合酶链反应分析显示，在 KO 小鼠未损伤和损伤的颈动脉中均未检测到 AT1 mRNA，而在野生型 (WT) 小鼠的未损伤颈动脉中则表达了 AT1 基因。受伤后 14 天，WT 小鼠受伤动脉中 AT1 mRNA 水平增加了 1.5 倍。尽管在未损伤的动脉中未检测到 AT2 mRNA，但在损伤后 2 周，两个动物组中均诱导了 AT2 基因的表达。血管损伤诱导 KO 小鼠和 WT 小鼠的新内膜形成。 WT和KO小鼠在组织学结果的范围上没有显着差异，例如新内膜和中膜的横截面积增加、增殖的平滑肌细胞的数量以及胶原蛋白和纤连蛋白的量。损伤后用低剂量的 Ang II 治疗可增强 WT 小鼠的新内膜生长，但不会增强 KO 小鼠的新内膜生长。此外，损伤前用选择性 AT1 拮抗剂 CV-11974 治疗仅在 WT 小鼠中显着减少了新内膜的形成，而损伤前用选择性 AT2 拮抗剂 PD-123319 治疗对两组动物均没有影响。这些结果表明 AT1 介导的 Ang II 信号传导对于新内膜形成的发展并不是必需的，尽管它可能会改变它。
Many studies using small-animal models suggest that angiotensin II (Ang II) plays an important role in neointimal formation after vascular injury. In the present study, we examined whether Ang II type 1 receptor (AT1)-mediated Ang II signaling is indispensable for the development of injury-induced neointimal formation using AT1a knockout (KO) mice. Reverse transcriptase-polymerase chain reaction analysis revealed that AT1 mRNA was not detectable in both uninjured and injured carotid arteries of KO mice, whereas the AT1 gene was expressed in uninjured carotid arteries of wild-type (WT) mice. At 14 days after injury, AT1 mRNA levels were increased by 1.5-fold in injured arteries of WT mice. Although AT2 mRNA was not detectable in uninjured arteries, expression of AT2 gene was induced in both animal groups at 2 weeks after injury. Vascular injury induced neointimal formation in KO mice as well as in WT mice. There were no significant differences between WT and KO mice in the extent of histological findings such as increased cross-sectional areas of the neointima and the media, the number of proliferating smooth muscle cells, and the amount of collagen and fibronectin. Treatment with subpressor doses of Ang II after injury enhanced the growth of neointima in WT mice but not in KO mice. Moreover, treatment with the selective AT1 antagonist CV-11974 before injury significantly decreased the formation of neointima in only WT mice, whereas treatment with the selective AT2 antagonist PD-123319 before injury had no effects in both animal groups. These results suggest that AT1-mediated Ang II signaling is not essential for the development of neointimal formation, although it may modify it.
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影响因子：
20.1
作者：
E. Su;D. Lombardi;J. Wiener;M. Daemen;M. Reidy;S. Schwartz
通讯作者：
E. Su;D. Lombardi;J. Wiener;M. Daemen;M. Reidy;S. Schwartz
α1-肾上腺素受体阻滞剂可减少大鼠胸主动脉和颈动脉中血管紧张素 II 诱导的血管平滑肌细胞 DNA 合成。
影响因子：
20.1
作者：
vanKleef,EM;Smits,JF;DeMey,JG;Cleutjens,JP;Lombardi,DM;Schwartz,SM;Daemen,MJ
通讯作者：
Daemen,MJ
血管紧张素 II 受体的分子生物学：概述。
DOI：
--
发表时间：
1994
期刊：
Journal of hypertension. Supplement : official journal of the International Society of Hypertension
影响因子：
--
作者：
Inagami,T;Guo,DF;Kitami,Y
通讯作者：
Kitami,Y
DOI：
10.1073/pnas.92.23.10663
发表时间：
1995-11-07
影响因子：
11.1
作者：
NAKAJIMA, M;HUTCHINSON, HG;DZAU, VJ
通讯作者：
DZAU, VJ
影响因子：
15.9
作者：
GIBBONS, GH;PRATT, RE;DZAU, VJ
通讯作者：
DZAU, VJ