In a recent study, researchers found that high levels of proteins associated with cellular aging in the blood and placenta are connected to peripartum cardiomyopathy (PPCM), a type of heart failure that occurs in late pregnancy or early postpartum. PPCM is a leading cause of maternal mortality. The new research, conducted by a team from Massachusetts General Hospital, sheds light on the underlying mechanisms of PPCM and suggests possible new treatment approaches.development. The findings are featured in Science Translational Medicine.
“Even though heart disease is now the leading cause of maternal death in the US, our understanding of the biology behind many of these conditions is still very limited,” said co-lead author Jason Roh, MD, MHS, a cardiologist who leads a cardiovascular aging laboratory at the Massachusetts General Hospital Cardiovascular Research Center. “Our research uncovers some fundamental aging-related biology that contributes to the onset of maternal heart failure during pregnancy and presents evidence from both patients and animal models.”
Roh and his colleagues conducted the study.The research team initially discovered that proteins secreted by aged cells were found in higher levels in the blood of young pregnant women with heart failure, which was unexpected. This led them to investigate whether these senescence proteins could be linked to the development of peripartum cardiomyopathy (PPCM) and preeclampsia, a hypertensive disorder of pregnancy that is a major risk factor for PPCM and postpartum heart failure. Their hypothesis was based on previous research.The researchers discovered that the placenta, which is a unique organ found only during pregnancy, shows signs of increased aging as the pregnancy nears its end.
When the team studied placentas from women with preeclampsia, they found that these placentas had multiple markers of accelerated aging and increased expression of many aging-related proteins. These proteins were also found in the blood of women with preeclampsia or PPCM.
One of the most abundant aging-related proteins found in these placentas was activin A, and higher levels of this protein were associated with more severe cases of the condition.Women with preeclampsia or PPCM may experience heart dysfunction or heart failure. According to Roh, the aging process of the placenta during pregnancy appears to be intensified in those who develop heart failure. This intensified aging process may cause the placenta to release certain substances into the mother’s blood that can have a negative impact on the heart’s function. In experiments with mice, it was found that the placentas of mice with PPCM had increased expression of proteins associated with cellular aging. Treating these mice with fisetin, a drug that can clear highly senescent cells, showed promising results.Specialized cells, towards the middle and end of pregnancy, partially decreased the aging of the placenta and improved the functioning of the heart. When the animals were treated with an antibody targeted at the activin A receptor after pregnancy, they experienced similar positive effects. “While we are still in the early stages of comprehending the impact of increased placental aging on the mother’s heart function, we believe our discoveries provide some essential insights into the biological aspects of heart failure during pregnancy,” Roh stated. “It is crucial to recognize that placental aging is a natural aspect of pregnancy. Understanding why this process becomes disrupted is important.”The next crucial steps in this research on pregnancy-related heart disease include determining how to safely regulate it before translating these findings.
