Pulmonary edema
Scientists Discover Potential New Treatment For Pulmonary Hypertension
Researchers at Indiana University and Notre Dame have discovered a potential new treatment for pulmonary hypertension, focusing on reversing vascular remodeling through an epigenetic pathway involving the protein SPHK2, as reported in Circulation Research. This innovative approach could transform the treatment of this serious lung condition.
Researchers at the Indiana University School of Medicine, at the school's South Bend regional campus, and their colleagues at the University of Notre Dame, have discovered a novel therapeutic target for treating pulmonary hypertension. This form of high blood pressure specifically impacts the blood vessels in the lungs. The team's research and findings have been recently published in the journal Circulation Research.
Pulmonary hypertension is a complex and often fatal condition that makes the heart work harder than normal to pump blood into the lungs. While the exact causes of pulmonary hypertension are unknown, one of its hallmarks is the thickening of the pulmonary blood vessels caused by an overgrowth of cells, also known as vascular remodeling.
New Therapeutic DiscoveriesMargaret A. Schwarz, MD, a professor of pediatrics at IU School of Medicine and senior author on the study, said there are few treatments for pulmonary hypertension, and they typically treat the symptoms of vascular remodeling rather than the remodeling itself.
Schwarz said what's exciting about her team's findings is the discovery of an epigenetic pathway mediated via the protein SPHK2 that can reduce and potentially reverse vascular remodeling in pulmonary hypertension.
Dushani Ranasinghe, PhD, left, and Margaret Schwarz, MD, at Ranasinghe's graduation ceremony from the University of Notre Dame. Credit: Courtesy of Margaret Schwarz
"This is one of the very first mechanisms of pulmonary hypertension identified that can be reversible," she said. "Normally, pulmonary hypertension patients are given medications to reduce the vascular pressure in the lungs or to help the heart squeeze better to pump blood, which are both symptoms of vascular remodeling. Our study looks at targeting the epigenetic reversal of this mechanism. Ultimately, the treatment would be to stop the vascular remodeling process entirely."
The concept is similar to cancer treatment, Schwarz said.
"In cancer, we stop tumor growth instead of just treating symptoms," she said. "Vascular remodeling is a different mechanism, but the idea is that the treatment would target the mechanism instead of the symptoms."
Key Findings and Future DirectionsOther key findings from the study include:
Schwarz and the study's first author, Dushani Ranasinghe, Ph.D., who was a member of Schwarz's lab while she was a graduate student at Notre Dame, were also interviewed about their findings for an episode of the "Discover CircRes" podcast, which is produced by Circulation Research.
Schwarz said the next steps for her research include further exploration of the SPHK2 protein as a therapeutic target for pulmonary hypertension, in collaboration with Brian Blagg, director of the Warren Center for Drug Discovery and Development at Notre Dame.
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
Other IU authors on the study include Maggie Holohan and Martin Gerig.
This study was made possible in part by funding from the National Institutes of Health, the Lilly Endowment, the O'Brien Family Endowment for Excellence, the National Science Foundation and the Buckner Family Scholarship.
Treating Altitude Sickness With Viagra
Sildenafil, the drug more commonly known as Viagra, may help with more than just sexual problems. Researchers say it can also ease the symptoms of altitude sickness. The finding could be significant because in severe cases, altitude sickness can cause dangerously high pulmonary arterial pressures and pulmonary edema, putting sufferers at significant risk of death.The study was conducted among 12 healthy men who were exposed to an altitude of about 14,000 feet. All were measured for physiological functioning at sea level and then again soon after arriving at a high altitude region in Europe. All the men showed some signs of elevated systolic pulmonary artery pressure after arriving at the high altitude region. Researchers then randomly assigned half the group to three daily doses of sildenafil. The other half received a placebo for comparison purposes.
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Results show sildenafil normalized systolic pulmonary artery pressure and men taking the placebo continued to have higher pressures. Researchers also noted no significant adverse effects in the men taking sildenafil thus they say that sildenafil may have a role to play in preventing altitude sickness.News Tagged With Pulmonary Artery
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