A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy
A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy
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DOI：
10.1016/j.cell.2006.12.036
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发表时间：
2007-02-09
期刊：
影响因子：
64.5
通讯作者：
Drexler, Helmut
中科院分区：
文献类型：
--
作者：
Hilfiker-Kleiner, Denise;Kaminski, Karol;Drexler, Helmut
产后心肌病（PPCM）是一种病因不明的疾病，产后死亡风险高。在这里，我们发现心肌细胞特异性缺失stat3的雌性小鼠发生PPCM。在这些小鼠中，心脏组织蛋白酶D （CD）的表达和活性增强，并与乳糜泻激素16 kDa形式的劈裂抗血管生成和促凋亡的产生有关。溴隐亭可抑制催乳素分泌，可阻止PPCM的发展，而强迫心肌产生16kda催乳素会损害心脏毛细血管网络和功能，从而重现PPCM的心脏表型。PPCM患者心肌STAT3蛋白水平降低，血清活化CD和16kda催乳素水平升高。因此，妊娠激素催乳素的生物活性衍生物介导PPCM，这意味着抑制催乳素的释放可能是PPCM的一种新的治疗策略。
Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology and exposes women to high risk of mortality after delivery. Here, we show that female mice with a cardiomyocyte-specific deletion of stat3 develop PPCM. In these mice, cardiac cathepsin D (CD) expression and activity is enhanced and associated with the generation of a cleaved antiangiogenic and proapoptotic 16 kDa form of the nursing hormone prolactin. Treatment with bromocriptine, an inhibitior of prolactin secretion, prevents the development of PPCM, whereas forced myocardial generation of 16 kDa prolactin impairs the cardiac capillary network and function, thereby recapitulating the cardiac phenotype of PPCM. Myocardial STAT3 protein levels are reduced and serum levels of activated CD and 16 kDa prolactin are elevated in PPCM patients. Thus, a biologically active derivative of the pregnancy hormone prolactin mediates PPCM, implying that inhibition of prolactin release may represent a novel therapeutic strategy for PPCM.