Peripartum cardiomyopathy (PPCM) is a serious form of heart failure that occurs late in pregnancy or early in the postpartum period and is a leading cause of maternal death. A recent study led by researchers from Massachusetts General Hospital sheds light on the mechanisms that contribute to the development of PPCM and suggests potential new therapeutic strategies. The study, published in Science Translational Medicine, focused on the role of senescent cells in PPCM and preeclampsia, a condition that increases the risk of developing PPCM.
The researchers found that proteins secreted by senescent cells were present at higher levels in the blood of young pregnant women with heart failure, leading them to investigate the potential role of these proteins in the development of PPCM and preeclampsia. Placental tissue from women with preeclampsia showed signs of increased senescence and higher expression of senescence proteins, particularly activin A. Higher levels of activin A were associated with more severe heart dysfunction in women with preeclampsia or PPCM, suggesting a link between placental senescence and maternal heart failure.
Experiments conducted in mice further supported the researchers’ findings, showing increased expression of senescence-associated proteins in the placentas of mice with PPCM. Treatment with fisetin, a drug that can clear senescent cells, during mid to late pregnancy improved heart function in these mice. Additionally, treatment with an antibody targeting the receptor for activin A after pregnancy had similar effects. These findings suggest that targeting placental senescence could be a promising approach to preventing or treating PPCM in pregnant women.
Although the study is in its early stages, the results provide important insights into the biology underlying heart failure in pregnancy. The researchers believe that understanding how amplified placental senescence affects maternal heart function is crucial for developing effective therapies for PPCM and related conditions. Further research is needed to determine how placental senescence is disrupted in pregnancy-related heart disease and how it can be safely regulated to improve outcomes for pregnant women at risk of developing PPCM.
Overall, the study highlights the importance of studying the role of senescent cells in pregnancy-related heart conditions and suggests that targeting placental senescence could be a promising avenue for developing new treatments for PPCM and preeclampsia. By understanding the underlying mechanisms driving maternal heart failure, researchers may be able to develop more effective therapies to improve outcomes for women at risk of developing these conditions during pregnancy. Further research is needed to fully understand the impact of placental senescence on maternal heart function and to develop safe and effective strategies to regulate this process.
