Endogenous estrogen attenuates hypoxia-induced pulmonary hypertension by inhibiting pulmonary arterial vasoconstriction and pulmonary arterial smooth muscle cells proliferation.
Endogenous estrogen attenuates hypoxia-induced pulmonary hypertension by inhibiting pulmonary arterial vasoconstriction and pulmonary arterial smooth muscle cells proliferation.
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内源性雌激素通过抑制肺动脉血管收缩和肺动脉平滑肌细胞增殖来减轻缺氧引起的肺动脉高压
DOI：
10.7150/ijms.5906
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发表时间：
2013
影响因子：
3.6
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Xu D;Niu W;Luo Y;Zhang B;Liu M;Dong H;Liu Y;Li Z
研究表明，外源性雌激素对包括缺氧引起的肺动脉高压（HPH）在内的多种疾病具有多种有益作用。然而，内源性雌激素对 HPH 的影响却很少被研究。在本研究中，我们探讨内源性雌激素对缺氧性肺动脉高压的保护作用和机制。将雄性、雌性、妊娠和去势大鼠置于低氧条件下饲养21天，然后测量血流动力学和肺循环形态指标。慢性缺氧暴露后，右心室收缩压、平均肺动脉压、右心室肥厚指数和动脉重塑指数显着升高。实验数据显示，雌性大鼠的严重程度较低，尤其是怀孕大鼠。在体外获得不同性别或发情周期大鼠的动脉环，然后进行动脉环实验，通过记录最大II期血管收缩来研究肺血管收缩情况。数据显示，发情前期雌性的血管收缩比发情间期雌性或雄性组的血管收缩更轻微，这可以通过治疗 U0126（一种 MAPK 通路抑制剂）来平衡。分离不同性别或发情周期大鼠的肺动脉平滑肌细胞，在2%氧气条件下培养24小时，通过[3H]-胸苷掺入法评价细胞增殖情况。发情前期大鼠的细胞比其他组表现出较低的增殖，U0126 和雷洛昔芬（一种选择性雌激素受体调节剂）可以抵消这种情况。检测血清雌二醇水平，水平较高的大鼠表现出肺动脉高压的严重程度较轻。总之，内源性雌激素可以通过非基因组机制减弱血管收缩并通过基因组和非基因组机制抑制平滑肌细胞增殖，从而减轻缺氧引起的肺动脉高压。
Exogenous estrogen was shown to exert various beneficial effects on multiple diseases including hypoxia-induced pulmonary hypertension (HPH). However, the effect of endogenous estrogen on HPH was seldom investigated. In the present study, we explored the protective effects and mechanisms of endogenous estrogen on hypoxia-induced pulmonary hypertension. Male, female, pregnant and ovariectomized rats were housed in a hypoxic condition for 21 days, and then hemodynamic together with morphologic indexes of pulmonary circulation were measured. The right ventricular systolic pressure, mean pulmonary artery pressure, right ventricular hypertrophy index, and arterial remodeling index were significantly elevated after chronic hypoxia exposure. Experimental data showed less severity in female, especially in pregnant rats. In vitro, artery rings of different sex or estrus cycle rats were obtained, and then artery rings experiments were performed to investigate pulmonary vasoconstriction by recording the maximum phase II vasoconstriction. Data showed that the vasoconstriction was milder in proestrus female than diestrus female or male groups, which could be leveled by treating U0126 (a MAPK pathway inhibitor). Pulmonary arterial smooth muscle cells isolated from different sex or estrus cycle rats were cultured in the condition of 2% oxygen for 24 hours, and cell proliferation was evaluated by the [3H]-thymidine incorporation assay. Cells from proestrus rats exhibited lower proliferation than the other groups, which could be countered by both U0126 and raloxifene (a selective estrogen receptor modulator). Serum estradiol levels were detected, and rats with higher levels showed less severity of pulmonary hypertension. Conclusively, endogenous estrogen may alleviate hypoxia-induced pulmonary hypertension by attenuating vasoconstriction through non-genomic mechanisms and inhibiting smooth muscle cells proliferation through both genomic and non-genomic mechanisms.
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影响因子：
3.3
作者：
Ji, Y.;Tang, B.;Traub, R. J.
通讯作者：
Traub, R. J.
影响因子：
--
作者：
Lee, Jennifer S.;Yaffe, Kristine;Lui, Li-Yung;Cauley, Jane;Taylor, Brent;Browner, Warren;Cummings, Steven
通讯作者：
Cummings, Steven
DOI：
10.1152/ajpendo.00201.2007
发表时间：
2007-09-01
影响因子：
5.1
作者：
Lahm, Tim;Patel, Ketan M.;Meldrum, Daniel R.
通讯作者：
Meldrum, Daniel R.
影响因子：
8.3
作者：
Dubey, RK;Gillespie, DG;Jackson, EK
通讯作者：
Jackson, EK
影响因子：
1.4
作者：
Cauchy, E;Chetaille, E;Marsigny, B
通讯作者：
Marsigny, B