Knockouts and transgenics confirm the importance of adrenomedullin in the vasculature.
Knockouts and transgenics confirm the importance of adrenomedullin in the vasculature.
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基因敲除和转基因证实了肾上腺髓质素在脉管系统中的重要性。
DOI：
10.1016/s0165-6147(00)01617-5
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发表时间：
2001
影响因子：
13.8
通讯作者：
D. Smith
中科院分区：
文献类型：
--
作者：
D. Hay;D. Smith
黛比湖Hay和大卫M. Smith他们的肾上腺髓质素过表达（AMOX）小鼠（图1）。使用内皮素-1启动子指导肾上腺髓质素合成到血管系统产生了平均血压降低而心率无变化的小鼠。抑制一氧化氮（NO）合酶（NOS）使这些小鼠的血压正常化，这支持了NO介导肾上腺髓质素作用的假设。AMOX小鼠对脂多糖介导的感染性休克的有害影响不太敏感6。此外，袖带诱导血管损伤的AMOX小鼠比野生型小鼠显示出更少的内膜增厚和细胞分裂，这两种作用都被NOS抑制剂阻断。在生殖系中缺失整个Adm基因的小鼠中，纯合敲除（Adm-PAMP-/-）在胚胎阶段被证明是致命的，这表明肾上腺髓质素在发育中的重要性。胚胎几乎没有卵黄囊血管化，脐带很细，胎盘中几乎没有完全形成的血管。血管造影显示，这些血管形成往往是泄漏。最有趣的是，这些敲除小鼠可以通过渗透性微型泵给予肾上腺髓质素来拯救。
Debbie L. Hay and David M. Smith their adrenomedullin overexpressing (AMOX) mouse (Fig. 1). Direction of adrenomedullin synthesis to the vasculature using the endothelin-1 promoter yielded mice with decreased mean blood pressure and no change in heart rate. Inhibition of nitric oxide (NO) synthase (NOS) normalized blood pressure in these mice, which supports the hypothesis that NO mediates the effects of adrenomedullin. AMOX mice were less susceptible to the detrimental effects of lipopolysaccharide-mediated septic shock6. Furthermore, AMOX mice with cuff-induced vascular injury showed less intimal thickening and cell division than wild-type mice, with both effects blocked by NOS inhibitors. In mice in which the entire Adm gene was deleted in the germ line, the homozygous knockout (Adm–PAMP−/−) proved lethal at the embryonic stage, which indicates the importance of adrenomedullin in development. Embryos had little yolk sac vascularization, thin umbilical cords and few fully formed vessels in the placenta. Angiography showed that those vessels that were formed tended to be leaky. Most interestingly, these knockout mice could be rescued by administration of adrenomedullin by osmotic mini-pump.
人肾上腺髓质素基因递送可防止高血压达尔盐敏感大鼠的心脏肥大、纤维化和肾损伤。
DOI：
10.1089/10430340050129440
发表时间：
2000
期刊：
Human gene therapy.
影响因子：
--
作者：
Zhang,JJ;Yoshida,H;Chao,L;Chao,J
通讯作者：
Chao,J