Nature：心脏血管生成失衡导致围产期心肌病

在尼日利亚和海地等国家，围产期心肌症（Peripartum cardiomyopathy，PPCM）影响着0.33‰-0.33%的怀孕女性。该疾病在怀孕的最后一个月或坐月子的前五个月会出现心脏收缩的心力衰竭等症状。虽然近一半的患者在坐月子期间可能会恢复心脏功能，但也有很多的病人发展为慢性心力衰竭，最终只好心脏移植或走向死亡。

5月9月，Nature在线发表了由贝斯以色列女执事医疗中心等多家机构合作的题为《Cardiac angiogenic imbalance leads to peripartum cardiomyopathy》的研究文章，阐明了导致怀孕女性患围产期心肌症的机制。

研究发现，PGC-1α （血管生成调节子）缺陷的小鼠导致严重的PPCM。然而，亲血管生成治疗可以使其恢复。

人类胎盘在妊娠晚期分泌可溶性的血管内皮生长因子（sFLT1），在多胎妊娠和子痫前期分泌更加突出。

抗血管生成的环境伴随着亚临床心脏功能紊乱，紊乱程度与心脏循环的sFLT1一致。外源的sFLT1单独作用引起小鼠心脏舒张的功能异常；然而外源的sFLT1单独作用心脏PGC-1α 缺陷的小鼠却导致心脏收缩的功能异常。

这些研究结果表明，PPCM是一种由怀孕期间产生的过高抗血管生成信号引起的血管疾病。

doi:10.1038/nature11040

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Cardiac angiogenic imbalance leads to peripartum cardiomyopathy

Ian S. Patten，Sarosh Rana，Sajid Shahul，Glenn C. Rowe，Cholsoon Jang，Laura Liu，Michele R. Hacker，Julie S. Rhee，John Mitchell，Feroze Mahmood，Philip Hess，Caitlin Farrell，Nicole Koulisis，Eliyahu V. Khankin，Suzanne D. Burke，Igor Tudorache，Johann Bauersachs，Federica del Monte，Denise Hilfiker-Kleiner，S. Ananth Karumanchi& Zoltan Arany

Abstract

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery， and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM， and why it is associated with pre-eclampsia， remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance， accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α， a powerful regulator of angiogenesis， develop profound PPCM. Importantly， the PPCM is entirely rescued by pro-angiogenic therapies. In humans， the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1)， and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction， the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice， and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally， plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease， caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis， and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.