Mitochondrial coupling factor 6 as a potent endogenous vasoconstrictor
Mitochondrial coupling factor 6 as a potent endogenous vasoconstrictor
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DOI：
10.1172/jci200111076
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发表时间：
2001-10-01
影响因子：
15.9
通讯作者：
Okumura, K
中科院分区：
文献类型：
--
作者：
Osanai, T;Tanaka, M;Okumura, K
我们最近证明，耦合因子 6（线粒体 ATP 合酶能量转导柄的重要组成部分）可抑制血管内皮细胞中前列环素的合成。在这里，我们测试了耦合因子 6 存在于细胞表面并参与体循环调节的假设。该肽存在于 CRL-2222 血管内皮细胞的表面，并由这些细胞释放到培养基中。在体内，该肽在大鼠的血管系统中循环，其基因表达和血浆浓度在自发性高血压大鼠（SHR）中高于正常血压对照组。用去甲肾上腺素升高血压并不影响耦合因子6的血浆浓度。静脉注射重组肽显然是通过抑制前列环素合成来升高血压，而耦合因子6的特异性抗体则随着血浆前列环素的增加而降低全身血压。有趣的是，用环氧合酶抑制剂吲哚美辛治疗可以消除该抗体的降血压作用。这些发现表明线粒体偶联因子 6 以循环激素的形式发挥有效的内源性血管收缩剂的作用，并可能提示高血压的新机制。
We demonstrated recently that coupling factor 6, an essential component of the energy-transducing stalk of mitochondrial ATP synthase, suppresses the synthesis of prostacyclin in vascular endothelial cells. Here, we tested the hypothesis that coupling factor 6 is present on the cell surface and is involved in the regulation of systemic circulation. This peptide is present on the surface of CRL-2222 vascular endothelial cells and is released by these cells into the medium. In vivo, the peptide circulates in the vascular system of the rat, and its gene expression and plasma concentration are higher in spontaneously hypertensive rats (SHRs) than in normotensive controls. Elevation of blood pressure with norepinephrine did not affect the plasma concentration of coupling factor 6. Intravenous injection of recombinant peptide increased blood pressure, apparently by suppressing prostacyclin synthesis, whereas a specific Ab to coupling factor 6 decreased systemic blood pressure concomitantly with an increase in plasma prostacyclin. Interestingly, the antibody's hypotensive effect could be abolished by treating with the cyclooxygenase inhibitor indomethacin. These findings indicate that mitochondrial coupling factor 6 functions as a potent endogenous vasoconstrictor in the fashion of a circulating hormone and may suggest a new mechanism for hypertension.