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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 Discoveries

Margaret 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 Directions

Other key findings from the study include:

SPHK2 can drive pulmonary hypertension pathogenesis via histone H3K9 hyperacetylation, contributing to pulmonary artery smooth muscle cell (PASMC) vascular remodeling.

SPHK2 deficiency confers reduced pulmonary vascular resistance, right ventricle hypertension, and distal vessel wall thickness.

EMAP (endothelial monocyte activating polypeptide) II has a key role in the stimulation of nuclear SPHK2/S1P epigenetic modulating axis, suggesting that cooperation between SPHK2 and

EMAPII could be a major driving force for epigenetic-mediated vascular PASMC reprogramming and remodeling in pulmonary hypertension.

Pulmonary vascular endothelial cells are a priming factor of the EMAPII/SPHK2/S1P axis that alters the acetylome with a specificity for PASMC, through hyperacetylation of histone H3K9.

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.

With These Hospital Go-bag Essentials, I'm Always Prepared

Living with a chronic illness feels like being caught in a revolving door of doctor appointments and surprise trips to the emergency room. Trust me, I've been caught there more times than I can count, all thanks to pulmonary hypertension (PH).

But amid the challenges, I've gained invaluable insights that I'm eager to share with you. And you know what? One of the most crucial lessons is to always be prepared with a hospital go-bag.

I know it's not as thrilling as packing for a mom-to-be hospitalization or a vacation, but believe me when I say that preparing a bag like this is an absolute game-changer.

In the past, I struggled to have the right things with me during hospital stays. My family members did their best to help, but sometimes they'd grab outdated items or clothes that no longer fit. They already have enough on their plates, from juggling work to visiting me in the hospital. After several hospitalizations, I worked to lighten their load by creating an essential list of must-haves for my stay.

Now, I have a trusty bag that's always fully stocked. Hopefully, you'll never experience the kind of urgent situation that necessitates a hospital go-bag that you grab in a rush, but sadly unexpected hospitalizations are all too common with a rare disease like PH. So when it comes to preparing, it's better to be safe than sorry.

So what's inside my hospital go-bag? The following is my master list. Remember that this list works for me, but you might find other items helpful for your go-bag. Fellow Pulmonary Hypertension News columnist Anna Jeter also wrote about prepping a go-bag, so check out her column in case her ideas are more fitting to your circumstances.

Clothing and toiletries

First things first, let's talk about clothing. Trust me, it's crucial to put careful thought into this and not instinctively grab your favorite items. Instead, pack the items that are best suited for the hospital.

I always pack at least three comfortable tank tops and two or three short-sleeved T-shirts. Because of hospital air conditioning, I'll also pack a long-sleeved T-shirt, pullover, or jacket.

For bottoms, I include two lightweight yoga-style pants, shorts for warmer months, and sweatpants for cooler months.

Pajama sets — button-up tops work best for IVs and heart monitors — are a must, along with enough underwear and sports bras for each day. And, of course, let's remember fuzzy socks, slippers, and flip-flops for ultimate comfort and hygiene.

Toiletries also are necessary, so I bring travel-sized liquid body soap, shampoo, conditioner, a hairbrush, detangler spray, facial moisturizer, and body lotion. My healthcare team always comments on how fresh my room smells, so these things aren't only for my benefit! Those Bath & Body Works lotions and body mists make a difference.

I also make sure to have extra hair ties, dry shampoo, toothpaste, a toothbrush, and feminine products.

Electronics and comfort items

Let's talk electronics, because it seems we can't live without them. I bring my trusty Kindle to unplug from more stimulating screens.

But as nice as a break from digital media is, it's also nice to have my phone, because connection to the outside world is essential to preventing painful feelings of isolation and disconnection.

It's good to have headphones and an iPad in case I'm sharing a room and a TV with someone. I also may carry my MacBook in case I needed to do some work. Instead of packing the usual chargers, I always pack a 6- to 10-foot phone charger to ensure the cord reaches my bed, plus an external charging block in case I'm wheeled to other areas of the hospital.

Comfort items? They make a world of difference. A few of my favorites include a cozy blanket to replace less comfortable hospital blankets, a pillow that's more fitting to my posture, earplugs to dull the sound of IV alarms at night, a sleep mask for when nurses do their late-night rounds, and a sound machine (if I'm lucky enough to have a private room) to help me sleep. These little things create a soothing environment that helps me relax.

Final things

Here's a little advice from someone who has learned the hard way: Pack more than you think you'll need, especially underwear! Plus, don't forget extra medications, as a particular hospital might not have access to your PH treatments due to stocking issues or pharmacy delays.

I rarely take my go-bag into the ER to prevent germ exposure, but I always keep it in the car in case hospital admission is necessary. Otherwise, it stays by the front door of my home for easy access whenever needed.

When I return home, I wash everything and put it back in my bag — or at least I should. Lately, I haven't been as proactive as I need to be with this task. (But thinking about my procrastination inspired me to write this column, so it worked out.)

Anyway, when I'm prepared, my family doesn't have to worry about finding the right items and I don't have to worry about going without my necessities and desired items. Isn't that peace of mind worth some planning, packing, and even laundry?

If I missed something, please let me know in the comments below. Let's support and help each other out! Together, we can make hospital stays much more comfortable.

Note: Pulmonary Hypertension News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Pulmonary Hypertension News or its parent company, BioNews, and are intended to spark discussion about issues pertaining to pulmonary hypertension.

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