| Title: |
Cardiac angiogenic imbalance leads to peripartum cardiomyopathy |
| Authors: |
Patten IS; Rana S; Shahul S; Rowe GC; Jang C; Liu L; Hacker MR; Rhee JS; Mitchell J; Mahmood F; Hess P; Farrell C; Koulisis N; Khankin EV; Burke SD; Tudorache I; Bauersachs J; del Monte F; Hilfiker-Kleiner D; Karumanchi SA; Arany Z. |
| Contributors: |
Patten IS; Rana S; Shahul S; Rowe GC; Jang C; Liu L; Hacker MR; Rhee JS; Mitchell J; Mahmood F; Hess P; Farrell C; Koulisis N; Khankin EV; Burke SD; Tudorache I; Bauersachs J; del Monte F; Hilfiker-Kleiner D; Karumanchi SA; Arany Z. |
| Publication Year: |
2012 |
| Collection: |
IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| Subject Terms: |
Angiogenesi; Peripartum Cardiomyopathy; PGC1a |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/22596155; info:eu-repo/semantics/altIdentifier/wos/WOS:000304099100034; volume:485; issue:7398; firstpage:333; lastpage:338; numberofpages:6; journal:NATURE; https://hdl.handle.net/11585/969114 |
| DOI: |
10.1038/nature11040 |
| Availability: |
https://hdl.handle.net/11585/969114; https://doi.org/10.1038/nature11040 |
| Accession Number: |
edsbas.77F4D821 |
| Database: |
BASE |