Resistance to Neointimal Hyperplasia and Fatty Streak Formation in Mice With Adrenomedullin Overexpression
Resistance to Neointimal Hyperplasia and Fatty Streak Formation in Mice With Adrenomedullin Overexpression
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肾上腺髓质素过度表达小鼠对新内膜增生和脂肪纹形成的抵抗力
DOI：
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
H. Kurihara
中科院分区：
文献类型：
--
作者：
Y. Imai;T. Shindo;K. Maemura;M. Sata;Yuichiro Saito;Y. Kurihara;M. Akishita;J. Osuga;S. Ishibashi;K. Tobe;H. Morita;Y. Oh;Toru Suzuki;H. Maekawa;K. Kangawa;N. Minamino;Y. Yazaki;R. Nagai;H. Kurihara
目的：几项体外研究表明肾上腺髓质素（AM）在血管损伤和脂肪条纹形成的发病机制中起重要作用。为了在体内验证这种可能性，我们用血管选择性过表达AM的转基因小鼠（AMTg小鼠）评估了2种实验模型。方法和结果：在股动脉上放置动脉周围袖带，在2至4周时，AMTg小鼠的新内膜形成程度低于野生型小鼠（28天，内膜/中膜面积比分别为0.45±0.14和1.31±0.41,P <0.001）。在AMTg小鼠中观察到的这种血管保护作用被N&ohgr抑制；-硝基精氨酸甲酯。通过将AMTg小鼠与载脂蛋白E敲除小鼠（ApoEKO小鼠）杂交，我们进一步研究了AM对高胆固醇血症诱导的脂肪条纹形成的影响。ApoEKO/AMTg小鼠脂肪条纹病变的形成程度明显小于ApoEKO小鼠（病变面积百分比分别为12.0±3.9%和15.8±2.8%,P <0.05）。此外，与ApoEKO小鼠相比，AMTg/ApoEKO小鼠的内皮依赖性血管舒张作为NO生成的指示性更强。综上所述，我们的数据表明AM在体内具有血管保护作用，这至少部分是由NO介导的。
Objective—Several in vitro studies have implicated that adrenomedullin (AM) plays an important role in the pathogenesis of vascular injury and fatty streak formation. To test this possibility in vivo, we evaluated 2 experimental models using transgenic mice overexpressing AM in a vessel-selective manner (AMTg mice). Methods and Results—Placement of a periarterial cuff on femoral arteries resulted in neointimal formation at 2 to 4 weeks to a lesser extent in AMTg mice than in their wild-type littermates (at 28 days, intima/media area ratio 0.45±0.14 versus 1.31±0.41, respectively;P <0.001). This vasculoprotective effect observed in AMTg mice was inhibited by N&ohgr;-nitro-l-arginine methyl ester. We further examined the effect of AM on hypercholesterolemia-induced fatty streak formation by crossing AMTg mice with apolipoprotein E knockout mice (ApoEKO mice). The extent of the formation of fatty streak lesions was significantly less in ApoEKO/AMTg mice than in ApoEKO mice (percent lesion area 12.0±3.9% versus 15.8±2.8%, respectively;P <0.05). Moreover, endothelium-dependent vasodilatation as indicative of NO production was superior in AMTg/ApoEKO mice compared with ApoEKO mice. Conclusions—Taken together, our data demonstrated that AM possesses a vasculoprotective effect in vivo, which is at least partially mediated by NO.
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影响因子：
15.9
作者：
Knowles, JW;Reddick, RL;Maeda, N
通讯作者：
Maeda, N
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
抑制新内膜血管病变的基因治疗：内皮细胞一氧化氮合酶基因的体内转移。
DOI：
10.1073/pnas.92.4.1137
发表时间：
1995
影响因子：
11.1
作者：
vonderLeyen,HE;Gibbons,GH;Morishita,R;Lewis,NP;Zhang,L;Nakajima,M;Kaneda,Y;Cooke,JP;Dzau,VJ
通讯作者：
Dzau,VJ
影响因子：
15.9
作者：
Moroi, M;Zhang, L;Huang, PL
通讯作者：
Huang, PL
影响因子：
5.3
作者：
PAIGEN, B;MORROW, A;WILLIAMS, RA
通讯作者：
WILLIAMS, RA