Estrogen inhibits mast cell chymase release to prevent pressure overload-induced adverse cardiac remodeling.
Estrogen inhibits mast cell chymase release to prevent pressure overload-induced adverse cardiac remodeling.
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DOI：
10.1161/hypertensionaha.114.04238
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发表时间：
2015-02
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影响因子：
--
通讯作者：
Janicki JS
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文献类型：
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作者：
Li J;Jubair S;Janicki JS
雌激素对心肌糜酶的调节以及糜酶对心脏重构的影响尚不清楚。为了验证雌激素通过抑制肥大细胞糜酶释放来预防压力超负荷诱导的不良心脏重塑的假设，在7周龄的完整和卵巢切除大鼠中进行了主动脉缩窄或假手术。在造成缩窄前三天，另外一组卵巢切除大鼠开始接受17β-雌二醇（一种糜酶抑制剂或肥大细胞稳定剂）。术后18天评估左心室功能、心肌细胞大小、胶原体积分数、肥大细胞密度和脱粒以及心肌和血浆糜酶水平。主动脉收缩导致心室肥厚的完整和卵巢切除组，而胶原体积分数增加，仅在卵巢切除大鼠。糜酶蛋白质含量增加，主动脉收缩的完整和卵巢切除组的增加幅度更大的卵巢切除大鼠。肥大细胞密度和脱颗粒，血浆糜酶水平和心肌活性转化生长因子-1水平的增加，主动脉缩窄只在卵巢切除大鼠。雌激素替代治疗可明显减轻心肌收缩增加的糜酶、肥大细胞密度和脱颗粒、血浆糜酶和心肌活性转化生长因子-1，并可防止心室肥厚和增加胶原体积分数。糜蛋白酶抑制剂减弱主动脉收缩引起的心室肥大和胶原体积分数在卵巢切除大鼠类似的雌激素替代。奈多罗米产生类似的效果，除了降低糜酶含量。我们的结论是雌激素抑制肥大细胞糜酶的释放是负责对心脏保护对横向主动脉缩窄引起的不良心脏重构。
Estrogen regulation of myocardial chymase and chymase effects on cardiac remodeling are unknown. To test the hypothesis that estrogen prevents pressure overload-induced adverse cardiac remodeling by inhibiting mast cell chymase release, transverse aortic constriction or sham surgery was performed in 7-week-old intact and ovariectomized rats. Three days prior to creating the constriction, additional groups of ovariectomized rats began receiving 17β-Estradiol, a chymase inhibitor, or a mast cell stabilizer. Left ventricular function, cardiomyocyte size, collagen volume fraction, mast cell density and degranulation, and myocardial and plasma chymase levels were assessed 18 days post-surgery. Aortic constriction resulted in ventricular hypertrophy in intact and ovariectomized groups while collagen volume fraction was increased only in ovariectomized rats. Chymase protein content was increased by aortic constriction in the intact and ovariectomized groups with the magnitude of the increase being greater in ovariectomized rats. Mast cell density and degranulation, plasma chymase levels and myocardial active transforming growth factor- 1 levels were increased by aortic constriction only in ovariectomized rats. Estrogen replacement markedly attenuated the constriction-increased myocardial chymase, mast cell density and degranulation, plasma chymase and myocardial active transforming growth factor- 1 as well as prevented ventricular hypertrophy and increased collagen volume fraction. Chymostatin attenuated the aortic constriction induced ventricular hypertrophy and collagen volume fraction in the ovariectomized rats similar to that achieved by estrogen replacement. Nedocromil yielded similar effects except for the reduction of chymase content. We conclude that the estrogen-inhibited release of mast cell chymase is responsible for the cardioprotection against transverse aortic constriction-induced adverse cardiac remodeling.