Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy

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 wit...

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Main Authors:	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, Phil, 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
Format:	Online
Language:	English
Published:	2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356917/

id	pubmed-3356917
recordtype	oai_dc
spelling	pubmed-33569172012-11-17 Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy 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, Phil 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 Article 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. 2012-05-09 /pmc/articles/PMC3356917/ /pubmed/22596155 http://dx.doi.org/10.1038/nature11040 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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, Phil 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
spellingShingle	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, Phil 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 Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy
author_facet	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, Phil 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
author_sort	Patten, Ian S.
title	Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy
title_short	Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy
title_full	Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy
title_fullStr	Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy
title_full_unstemmed	Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy
title_sort	cardiac angiogenic imbalance leads to peri-partum cardiomyopathy
description	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.
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356917/
_version_	1611531493660688384

Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy

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