THE ANGIOTENSIN-II TYPE-2 (AT(2)) RECEPTOR ANTAGONIZES THE GROWTH EFFECTS OF THE AT(1) RECEPTOR - GAIN-OF-FUNCTION STUDY USING GENE-TRANSFER
THE ANGIOTENSIN-II TYPE-2 (AT(2)) RECEPTOR ANTAGONIZES THE GROWTH EFFECTS OF THE AT(1) RECEPTOR - GAIN-OF-FUNCTION STUDY USING GENE-TRANSFER
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DOI：
10.1073/pnas.92.23.10663
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发表时间：
1995-11-07
影响因子：
11.1
通讯作者：
DZAU, VJ
中科院分区：
文献类型：
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作者：
NAKAJIMA, M;HUTCHINSON, HG;DZAU, VJ
1型血管紧张素II(AT(1))受体已被很好地描述，但2型(AT(2))受体仍是一个谜。我们通过将AT(2)受体表达载体导入球囊损伤的大鼠颈动脉，验证了AT(2)受体可以调节血管平滑肌细胞生长的假说，并观察到AT(2)受体的过度表达抑制了新生内膜的形成。在培养的平滑肌细胞中，AT(2)受体的转染抑制了细胞的增殖并抑制了丝裂原活化蛋白激酶的活性。此外，我们还证实了AT(2)受体介导了妊娠后期主动脉DNA合成的发育调节性减少。这些结果表明，AT(2)受体具有抗增殖作用，拮抗AT(1)受体的生长作用。
The type 1 angiotensin II (AT(1)) receptor is well characterized but the type 2 (AT(2)) receptor remains an enigma. We tested the hypothesis that the AT(2) receptor can modulate the growth of vascular smooth muscle cells by transfecting an AT(2) receptor expression vector into the balloon-injured rat carotid artery and observed that overexpression of the AT(2) receptor attenuated neointimal formation. In cultured smooth muscle cells, AT(2) receptor transfection reduced proliferation and inhibited mitogen-activated protein kinase activity. Furthermore, we demonstrated that the AT(2) receptor mediated the developmentally regulated decrease in aortic DNA synthesis at the latter stages of gestation. These results suggest that the AT(2) receptor exerts an antiproliferative effect, counteracting the growth action of AT(1) receptor.