Cardiac angiogenic imbalance leads to peripartum cardiomyopathy.
Nature
; 485(7398): 333-8, 2012 May 09.
Article
em En
| MEDLINE
| ID: mdl-22596155
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Complicações Cardiovasculares na Gravidez
/
Cardiomiopatias
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Nature
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos