Cardiac angiogenic imbalance leads to peripartum cardiomyopathy.
Cardiac angiogenic imbalance leads to peripartum cardiomyopathy.
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DOI：
10.1038/nature11040
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发表时间：
2012-05-09
期刊：
影响因子：
64.8
通讯作者：
Arany, Zoltan
中科院分区：
文献类型：
--
作者：
Patten, Ian S.;Rana, Sarosh;Shahul, Sajid;Rowe, Glenn C.;Jang, Cholsoon;Liu, Laura;Hacker, Michele R.;Rhee, Julie S.;Mitchell, John;Mahmood, Feroze;Hess, Philip;Farrell, Caitlin;Koulisis, Nicole;Khankin, Eliyahu V.;Burke, Suzanne D.;Tudorache, Igor;Bauersachs, Johann;del Monte, Federica;Hilfiker-Kleiner, Denise;Karumanchi, S. Ananth;Arany, Zoltan
围产期心肌病(PPCM)是一种经常影响临产妇女的致命疾病，更常发生在先兆子痫和/或多胎妊娠的妇女中。PPCM的病因，或为什么它与先兆子痫有关，目前仍不清楚。我们在这里表明，PPCM与全身性血管生成失衡有关，先兆子痫加重了这种失衡。缺乏心脏pgc-1α(一种强大的血管生成调节器)的小鼠，会发展成深刻的pPCM。重要的是，PPCM完全可以通过促血管生成疗法来挽救。在人类，妊娠晚期的胎盘会分泌血管内皮生长因子抑制物，如可溶性Flt1(SFlt1)，多胎妊娠和先兆子痫会加剧这种情况。这种抗血管生成的环境伴随着亚临床心功能障碍，其程度与sFlt1的循环水平有关。外源性sFlt1单独导致野生型小鼠的舒张期功能障碍，以及缺乏心脏pgc-1α的小鼠严重的收缩功能障碍。最后，PPCM患者的血浆样本中含有异常高水平的sFlt1。这些数据有力地表明，PPCM在很大程度上是一种血管疾病，由围产期过多的抗血管生成信号引起。这些数据还解释了妊娠晚期如何对心脏动态平衡构成威胁，以及为什么先兆子痫和多胎妊娠是PPCM发展的重要风险因素。
Peri-partum cardiomyopathy (PPCM) is a frequently fatal disease that affects women near delivery, and occurs more frequently in women with pre-eclampsia and/or multiple gestation. The etiology of PPCM, or why it associates with pre-eclampsia, remains unknown. We show here 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 sub-clinical cardiac dysfunction, the extent of which correlates with circulating levels of sFlt1. Exogenous sFlt1 alone caused diastolic dysfunction in wildtype 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 strongly suggest that PPCM is in large part a vascular disease, caused by excess anti-angiogenic signaling in the peri-partum 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.
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DOI：
10.1073/pnas.0603615103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Arany, Zoltan;Novikov, Mikhail;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
8.9
作者：
Fett, JD;Christie, LG;Murphy, JG
通讯作者：
Murphy, JG
影响因子：
15.9
作者：
Handschin, Christoph;Choi, Cheol Soo;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
9.8
作者：
Bdolah, Yuval;Lam, Chun;Karumanchi, S. Ananth
通讯作者：
Karumanchi, S. Ananth
影响因子：
37.8
作者：
DEMAKIS, JG;RAHIMTOOLA, SH
通讯作者：
RAHIMTOOLA, SH