Increased angiotensin II type 1 receptor expression in hypercholesterolemic atherosclerosis in rabbits.
Increased angiotensin II type 1 receptor expression in hypercholesterolemic atherosclerosis in rabbits.
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兔高胆固醇血症动脉粥样硬化中血管紧张素 II 1 型受体表达增加。
DOI：
10.1161/01.atv.18.9.1433
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
J. Mehta
中科院分区：
文献类型：
--
作者：
Baichun Yang;M. Phillips;D. Mohuczy;Hongbin Meng;Leping Shen;P. Mehta;J. Mehta
血管紧张素II（Ang II）促进血管平滑肌生长，并可能参与动脉粥样硬化的发生和发展。为了研究在动脉粥样硬化中血管组织中Ang II受体的表达是否改变，雄性新西兰白兔分别给予高胆固醇饮食（1%胆固醇 + 4%椰子油与常规饲料混合；高胆固醇组，n = 12）或常规饲料（对照组，n = 8）喂养10周。在此期间结束时，高胆固醇饮食喂养的兔子血清胆固醇水平高于对照组（3616 ± 144比30 ± 1 mg/dL，P < 0.001）。对照组的主动脉没有动脉粥样硬化，而高胆固醇组51 ± 6%的主动脉被动脉粥样硬化覆盖。高胆固醇兔动脉粥样硬化主动脉组织中Ang II受体总表达量增加了5倍（292 ± 28比51 ± 32 fmol/mg组织，均值 ± 标准误，P < 0.001），并且Ang II受体表达增加完全是由于血管紧张素II 1型（AT1）受体表达增强（289 ± 38比38 ± 18 fmol/mg，P < 0.001），因为血管紧张素II 2型受体表达未改变（7 ± 5比3 ± 2 fmol/mg，P = 无显著差异）。通过特异性单克隆和多克隆AT1受体抗体进行免疫组织化学检测确定，AT1受体主要定位于动脉粥样硬化主动脉的中膜，在一定程度上也位于内膜。逆转录 - 聚合酶链反应证实了动脉粥样硬化组织中AT1受体mRNA合成增加。为了评估AT1受体表达增加的功能意义，检测了主动脉环对Ang II的收缩反应，发现动脉粥样硬化主动脉环的收缩反应明显增强（与对照主动脉环相比，P < 0.01）。高胆固醇兔主动脉环的内皮依赖性舒张明显减弱（P < 0.001）。这项研究表明，兔的高胆固醇血症导致动脉粥样硬化、内皮依赖性舒张丧失以及主动脉组织中Ang II受体（完全是AT1受体）表达增加，这可能导致血管反应性改变。
Angiotensin II (Ang II) promotes vascular smooth muscle growth and may be involved in the initiation and progression of atherosclerosis. To examine whether Ang II receptor expression in vascular tissues is altered in atherosclerosis, male New Zealand White rabbits were fed a high-cholesterol diet (1% cholesterol + 4% coconut oil mixed with regular chow; hypercholesterolemic group, n=12) or regular chow (control group, n=8) for 10 weeks. At the end of this period, the serum cholesterol level in the rabbits fed the high-cholesterol diet was higher than that in the control group (3616 +/- 144 versus 30 +/- 1 mg/dL, P<0.001). There was no atherosclerosis in the aortas of the control group, whereas 51 +/- 6% of the aorta was covered with atherosclerosis in the hypercholesterolemic group. Total Ang II receptor expression in the atherosclerotic aortic tissues was increased 5-fold in the hypercholesterolemic rabbits (292 +/- 28 versus 51 +/- 32 fmol/mg tissue, mean +/- SE, P<0.001), and the increased Ang II receptor expression was entirely due to enhanced Ang II type 1 (AT1) receptor expression (289 +/- 38 versus 38 +/- 18 fmol/mg, P<0.001), as Ang II type 2 receptor expression was unaltered (7 +/- 5 versus 3 +/- 2 fmol/mg, P=NS). AT1 receptors were localized primarily in the media and to some extent in the intima of the atherosclerotic aorta, as determined by immunohistochemistry with specific monoclonal and polyclonal AT1 receptor antibodies. Increased synthesis of AT1 receptor mRNA in atherosclerotic tissues was confirmed by reverse transcription-polymerase chain reaction. To evaluate the functional significance of increased AT1 receptor expression, the constrictor response of aortic rings to Ang II was examined and found to be markedly enhanced in atherosclerotic aortic rings (P<0.01 versus control aortic rings). The endothelium-dependent relaxation of aortic rings from hypercholesterolemic rabbits was markedly attenuated (P<0.001). This study shows that hypercholesterolemia in rabbits results in atherosclerosis, loss of endothelium-dependent relaxation, and increased Ang II receptor (entirely AT1 receptor) expression in aortic tissues, which may result in altered vasoreactivity.
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DOI：
10.1001/jama.1996.03540110036029
发表时间：
1996-09
期刊：
JAMA
影响因子：
--
作者：
M. Stampfer;R. Krauss;Jing Ma;P. Blanche;L. Holl;F. Sacks;C. Hennekens
通讯作者：
M. Stampfer;R. Krauss;Jing Ma;P. Blanche;L. Holl;F. Sacks;C. Hennekens
影响因子：
15.9
作者：
Rajagopalan, S;Kurz, S;Harrison, DG
通讯作者：
Harrison, DG
影响因子：
15.9
作者：
DUBEY, RK;JACKSON, EK;LUSCHER, TF
通讯作者：
LUSCHER, TF
血管紧张素 II 诱导脑神经元中血管紧张素 1 型 (AT1) 受体的核靶向。
DOI：
10.1210/endo.139.1.5679
发表时间：
1998
期刊：
Endocrinology.
影响因子：
--
作者：
Lu,D;Yang,H;Shaw,G;Raizada,MK
通讯作者：
Raizada,MK
近端小管上皮中存在的兔肾皮质 AT1 血管紧张素 II 受体的克隆。
DOI：
10.1152/ajprenal.1993.264.4.f645
发表时间：
1993
期刊：
The American journal of physiology
影响因子：
--
作者：
Burns,KD;Inagami,T;Harris,RC
通讯作者：
Harris,RC