Endoglin regulates nitric oxide-dependent vasodilatation
Endoglin regulates nitric oxide-dependent vasodilatation
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DOI：
10.1096/fj.03-0197fje
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发表时间：
2004-01-01
期刊：
影响因子：
4.8
通讯作者：
López-Novoa, IM
中科院分区：
文献类型：
--
作者：
Jerkic, M;Rivas-Elena, JV;López-Novoa, IM
Endoglin是一种膜糖蛋白，在心血管发育和血管生成中发挥重要作用。我们通过测量单倍体缺陷小鼠(Eng(+/-))及其子代Eng(+/+)仔鼠的一氧化氮(NO)依赖的血管扩张功能，研究了endoglin在血管张力控制中的作用。评估了乙酰胆碱、缓激肽和硝普钠对麻醉小鼠、离体鼠后肢和主动脉环的血管扩张作用。在ENG(+/+)小鼠中，乙酰胆碱和缓激肽引起的显著降压和血管扩张反应显著降低。两种动物对硝普钠的反应相似，提示血管扩张作用不足不是由于NO反应障碍所致。Eng(+/-)组小鼠尿和血浆中NO代谢产物亚硝酸盐的浓度低于Eng(+/+)组。ENG(+/-)组小鼠肾脏和股动脉内皮型一氧化氮合酶(ENOS)的表达水平约为ENG(+/+)组的一半，原代培养的ENG(+/-)组大鼠主动脉内皮细胞的eNOS水平也低于ENG(+/+)组。此外，Endoglin在培养细胞中的过表达或抑制分别导致eNOS蛋白水平的显著升高或降低。因此，我们在体内和体外的结果表明，内皮素林与NO依赖的血管扩张之间存在关系，这种关系是通过调节eNOS的表达来实现的。
Endoglin is a membrane glycoprotein that plays an important role in cardiovascular development and angiogenesis. We examined the role of endoglin in the control of vascular tone by measuring nitric oxide (NO)-dependent vasodilation in haploinsufficient mice (Eng(+/-)) and their Eng(+/+) littermates. The vasodilatory effect of acetylcholine, bradykinin, and sodium nitroprusside was assessed in anesthetized mice; in isolated, perfused hindlimbs; and in aortic rings. The substantial hypotensive and vasodilatory response induced by acetylcholine and bradykinin in Eng(+/+) was markedly reduced in Eng(+/-) mice. Both kinds of animals had similar responses to sodium nitroprusside, suggesting that the deficient vasodilatory effect is not due to a NO response impairment. Urinary and plasma concentrations of nitrites, a NO metabolite, were lower in Eng(+/-) than in Eng(+/+) mice. The levels of endothelial nitric oxide synthase (eNOS) in kidneys and femoral arteries were about half in Eng(+/-) than in Eng(+/+) mice and were also reduced in primary cultures of aortic endothelial cells from Eng(+/-) compared with those from Eng(+/+) mice. Furthermore, overexpression or suppression of endoglin in cultured cells induced a marked increase or decrease in the protein levels of eNOS, respectively. Thus, our results in vivo and in vitro demonstrate a relationship between endoglin and NO-dependent vasodilation mediated by the regulation of eNOS expression.