Sept. 10, 2025 | Austin, Minn. — Pulmonary arterial hypertension (PAH), a specific type of pulmonary hypertension, is a disease with a high mortality rate of 60-70% within five years of diagnosis. Many processes underlying pulmonary hypertension are poorly understood, which limits our ability to effectively treat it. The lab of Assistant Professor Aleksandra Babicheva, PhD, at The Hormel Institute, University of Minnesota, recently uncovered a role calcium may play in PAH progression. Dr. Babicheva and Postdoctoral Associate Ibrahim Elmadbouh, PhD, have co-authored a paper on their findings in the scientific journal American Journal of Physiology-Lung Cellular and Molecular Physiology.
PAH starts when the slow-growing cells that line blood vessels, called endothelial cells, change into a different kind of cell that grows and divides at rapid, uncontrolled rates—similar to the way cancer cells do. Normally, these cells form a thin, one-cell layer inside blood vessels. As PAH sets in, the blood vessels become increasingly obstructed, forcing the heart to work harder to push blood through them. For people with PAH, everyday activities, like climbing stairs or light exercise, become an increasingly harder struggle for breath as the disease worsens. Ultimately, all the extra strain on the heart can lead to heart failure.
“The drugs and treatment options we have for PAH right now, they’re not really treating the disease, they’re helping the patient maintain a quality of life at a certain level. Mortality is still unacceptably high,” Dr. Babicheva said.
Part of the problem, she explained, has to do with where we’ve been looking for answers.
“What we have studied for the last couple decades, it’s all been about smooth muscle cells, but that’s not the whole story. That didn’t lead to therapeutically effective treatments for patients. I think we need to try something different,” Dr. Babicheva said.
For the Babicheva Lab, that “something different” could be which cells are targeted for PAH treatment. For decades, calcium has been targeted in the development of treatments for pulmonary hypertension due to its detrimental role in smooth muscle cells. Contrarily, calcium’s role in endothelial cells has been considered beneficial. However, the Babicheva Lab’s study demonstrated endothelial calcium is likely involved in the development of pulmonary hypertension—which could be key to developing more effective treatments for patients.
Aiming to uncover what goes wrong in these endothelial cells, the Babicheva Lab designed a study to analyze specific molecules that play a role in the process of calcium signaling, which forms the calcium channels that allow calcium to enter a cell from the outside. When those molecules were blocked and calcium could no longer enter the cell, they found it prevented the abnormal proliferative behavior that cells take on in pulmonary hypertension.
The study was conducted in collaboration with researchers at Mayo Clinic and the University of California San Diego Department of Medicine.
Progress through collaboration
While in PAH, erratic cells remain within the lungs and don’t metastasize the way cancer cells do, it does share other similarities with the disease. Sometimes, due to those commonalities, cancer studies can yield ideas for future PAH studies, as they did here.
“This paper is actually the first paper for our disease, pulmonary hypertension, to show that calcium is important in endothelial cells. But this similar mechanism is also happening in cancer cells, and that’s been studied in that field for decades. So, we can look at cancer ideas for new ideas to try. Sometimes it works in our cells, or sometimes the mechanisms are different. Similar also to clinical trials: sometimes anticancer drugs also have promising results in pulmonary hypertension patients.”
Dr. Babicheva hopes their recent work can further accelerate research progress in this area and generate new research questions and ideas that ultimately provide better treatment options to patients who have PAH.
“This can act as fertilized ground for other investigators to dig deeper in this area. I hope, after this paper is published, that more people consider studying this area. It’s very important if we want to break through and develop solutions with therapeutic potential for pulmonary hypertension,” Dr. Babicheva said.
Read the paper here: https://doi.org/10.1152/ajplung.00400.2024
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ABOUT THE HORMEL INSTITUTE
Founded in 1942 by Jay C. Hormel and The Hormel Foundation, The Hormel Institute, University of Minnesota, makes scientific advancements that enhance wellbeing and extend human life. For more than 80 years, we have pursued our mission to conduct research and provide education in the biological sciences with applications in medicine and agriculture. A part of the University of Minnesota's Research and Innovation Office, The Hormel Institute partners with the region's leading biomedical research facilities, including Mayo Clinic.