Michelle Matter, PhD, investigator at The Lundquist Institute for Biomedical Innovation, and her lab have identified disruptions in cell stress-response and protein quality-control pathways in peripartum cardiomyopathy (PPCM), a rare but life-threatening form of heart failure that develops during late pregnancy or in the months following childbirth.
The findings, published in Cells, offer new insight into what may be happening in the heart when it can no longer keep up with the physical demands of pregnancy and postpartum recovery. PPCM weakens the heart and makes it harder for the body to pump blood. The condition can be difficult to recognize because symptoms such as fatigue, swelling, and shortness of breath may resemble normal pregnancy-related changes. In severe cases, PPCM can lead to life-threatening heart failure.
In this study, Dr. Matter’s team performed transcriptome-wide RNA sequencing on PPCM patients and healthy control heart tissue samples and analyzed the resulting gene-expression data. “Our goal was to understand how pregnancy-associated stress reshapes molecular signaling in the failing maternal heart,” said Dr Matter. “What emerged was evidence of coordinated disruption across pathways responsible for maintaining protein quality control, mitochondrial function, and cardiomyocyte stress adaptation.”
One major takeaway is that the heart’s “quality control” system are impaired. Healthy cells constantly make, fold, repair, and remove proteins, which act like tiny machines that keep the cell running. When this cleanup and repair system stops working properly, damaged proteins build up and place added stress on heart cells.
The researchers observed strong activation of integrated stress-response pathways, alongside evidence of mitochondrial dysfunction that may compromise the heart’s ability to adapt to the increased metabolic demands of pregnancy. First author Pooja Choubey, PhD, stressed “the data suggest that PPCM involves the convergence of multiple stress-related processes rather than a single pathogenic mechanism. By understanding how stress-response systems fail in PPCM, we hope to move closer to strategies that can protect the maternal heart before irreversible damage occurs.”
While more research is needed before these findings lead to new treatments, the study points scientists toward promising areas for future investigation. Better understanding these cell stress signals could one day help researchers develop earlier tests, identify women at higher risk, or design therapies to protect the heart before serious damage occurs.
This work adds to The Matter Lab’s ongoing research into how the maternal heart adapts to pregnancy and why that process sometimes fails. By uncovering what goes wrong at the cellular level, her team is helping move the field closer to better care for mothers affected by pregnancy-related heart failure.