A team of scientists from Indiana University and the University of Notre Dame has made a significant breakthrough in the treatment of pulmonary hypertension. Their research, published in Circulation Research, focuses on an epigenetic mechanism that utilizes the SPHK2 protein to reverse vascular remodeling, a key aspect of this severe lung disease.
The study, conducted by researchers from Indiana University School of Medicine’s South Bend regional campus and their Notre Dame counterparts, introduces an innovative therapeutic target for pulmonary hypertension. This condition, a specific form of high blood pressure, affects the lung’s blood vessels and has been challenging to treat due to its complexity and potentially fatal outcomes.
Pulmonary hypertension is characterized by an increased workload on the heart, forcing it to pump blood into the lungs more strenuously. The condition often involves the thickening of pulmonary blood vessels due to cellular overgrowth, known as vascular remodeling. The exact causes of this disease are still not fully understood.
Innovative Therapeutic Insights
Dr. Margaret A. Schwarz, MD, a pediatrics professor at the IU School of Medicine and the study’s senior author, emphasized the limited treatment options for this condition, which mainly address the symptoms of vascular remodeling. Her team’s groundbreaking discovery revolves around an epigenetic pathway controlled by the SPHK2 protein, which shows promise in reducing and potentially reversing the vascular remodeling in pulmonary hypertension.
Schwarz highlights the groundbreaking nature of their discovery, likening the approach to cancer treatment where the focus is on halting tumor growth rather than merely treating symptoms. Similarly, this new method aims to target the mechanism of vascular remodeling rather than its symptoms.
Critical Discoveries and Prospects
Key findings from this research include:
- SPHK2’s role in driving pulmonary hypertension through histone H3K9 hyperacetylation, influencing vascular remodeling in pulmonary artery smooth muscle cells (PASMC).
- Decreased pulmonary vascular resistance and right ventricle hypertension in SPHK2-deficient models, along with reduced thickness of distal vessel walls.
- The crucial involvement of EMAP II in stimulating the nuclear SPHK2/S1P epigenetic axis, indicating a significant role in PASMC vascular remodeling.
- The impact of pulmonary vascular endothelial cells in priming the EMAPII/SPHK2/S1P axis, specifically altering PASMC through histone H3K9 hyperacetylation.
Dr. Schwarz, along with the study’s first author, Dr. Dushani Ranasinghe, Ph.D., discussed these findings on the “Discover CircRes” podcast. The next phase of Schwarz’s research involves further investigation of the SPHK2 protein as a therapeutic target, in collaboration with Brian Blagg from Notre Dame’s Warren Center for Drug Discovery and Development.
This study, which also involved contributions from other IU researchers like Maggie Holohan and Martin Gerig, received support from various sources, including the National Institutes of Health, the Lilly Endowment, the O’Brien Family Endowment for Excellence, the National Science Foundation, and the Buckner Family Scholarship.
Reference: “Altered Smooth Muscle Cell Histone Acetylome by the SPHK2/S1P Axis Promotes Pulmonary Hypertension” by A. Dushani C.U. Ranasinghe, Maggie Holohan, Kalyn M. Borger, Deborah L. Donahue, Rafael D. Kuc, Martin Gerig, Andrew Kim, Victoria A. Ploplis, Francis J. Castellino and Margaret A. Schwarz, 12 September 2023, Circulation Research. DOI: 10.1161/CIRCRESAHA.123.322740
Frequently Asked Questions (FAQs) about Pulmonary Hypertension Treatment
What is the new breakthrough in treating pulmonary hypertension?
Researchers from Indiana University and the University of Notre Dame have discovered a new treatment approach for pulmonary hypertension. It involves reversing vascular remodeling through an epigenetic pathway mediated by the SPHK2 protein, as detailed in their study published in Circulation Research.
How does the new treatment for pulmonary hypertension work?
The treatment targets the reversal of vascular remodeling, a key factor in pulmonary hypertension, through an epigenetic pathway involving the SPHK2 protein. This approach focuses on the underlying mechanism rather than just treating the symptoms of the disease.
What makes this pulmonary hypertension treatment approach unique?
This approach is unique because it targets the epigenetic reversal of vascular remodeling in pulmonary hypertension, a method similar to how certain cancer treatments focus on stopping tumor growth instead of just addressing the symptoms.
What are the key findings of the study on pulmonary hypertension?
Key findings include the role of the SPHK2 protein in driving pulmonary hypertension through histone H3K9 hyperacetylation, influencing vascular remodeling in pulmonary artery smooth muscle cells. It also highlights the potential of SPHK2 deficiency in reducing pulmonary vascular resistance and right ventricle hypertension.
Who conducted the research on this new pulmonary hypertension treatment?
The research was conducted by a team from Indiana University School of Medicine and the University of Notre Dame, with significant contributions from Dr. Margaret A. Schwarz, MD, a professor of pediatrics at IU School of Medicine, and Dr. Dushani Ranasinghe, Ph.D.
More about Pulmonary Hypertension Treatment
- Circulation Research Study
- Indiana University School of Medicine
- University of Notre Dame Research
- SPHK2 Protein and Pulmonary Hypertension
- Vascular Remodeling in Pulmonary Hypertension
- Epigenetic Pathways in Medical Research
- National Institutes of Health Funding
- Pulmonary Hypertension Therapies