New AHA-funded Project at Virginia Tech Looks to RNA for Therapies

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by Vanda Pinto, PhD |

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Note: This story was updated Aug. 11, 2021, to clarify that the researchers are not affiliated with the Virginia Tech Carilion School of Medicine.

Two new researchers at Virginia Tech will be focusing their studies on the mechanisms of heart and vascular diseases — including the role of RNA molecules in pulmonary arterial hypertension (PAH) — and already have American Heart Association (AHA) funding for their projects.

Both Yassine Sassi, PhD, and Jessica Pfleger, PhD, hope their work can lead to new treatments for PAH and other disorders, they said in a university press release.

“Despite decades of research, [PAH] remains incurable,” said Sassi, who, along with Pfleger, will serve as an assistant professor at the Fralin Biomedical Research Institute.

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Sassi, who will work in the institute’s center for vascular and heart research, is investigating the role of short RNA molecules — called microRNAs — in PAH. He believes that targeting these molecules could be therapeutically beneficial for people with this rare type of pulmonary hypertension.

The AHA recently awarded Sassi its Transformational Project Award for his work.

“New approaches to treating [PAH] are desperately needed,” said Sassi, also an assistant professor at the Virginia-Maryland College of Veterinary Medicine. There he is part of the department of biomedical sciences and pathobiology.

In PAH, the narrowing of the arteries that go from the heart to the lungs leads to high blood pressure. Available treatments are intended to slow its progression and ease symptoms, but the disease has no cure.

Sassi hypothesizes that microRNAs, short stretches of non-coding RNA that bind to messenger RNA, are involved in changes in pulmonary arteries and cause high blood pressure.

His aim is to understand whether blocking a microRNA — one which he and colleagues identified — can subsequently reverse these alterations, thereby revealing an innovative strategy for developing a new PAH therapy.

In a study published in 2019, Sassi and his team discovered a hidden pathway between cells in the lungs that a molecule uses to protect the heart from damage due to pulmonary hypertension, according to a separate press release.

The scientist also is working on treatments for pulmonary fibrosis, a related condition.

“There has been intense research into these diseases in the last 20 years, but they still have high morbidity and high mortality,” said Sassi, whose work will focus on “new directions and therapies to improve understanding and treatment of these two diseases.”

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Pfleger, meanwhile, will be studying why heart cells under stress become resistant to the hormone insulin. Insulin allows glucose, a source of energy, to enter cells and be used for their function.

Her project, also funded by the AHA, will focus on how metabolism and stress alter gene activity in the heart. Metabolism involves all the chemical processes that sustain life, such as breathing, and food digestion.

In heart disease, Pfleger hypothesizes, gene activity in heart cells is altered, which causes resistance to insulin. She believes that a molecule called REDD1 is responsible for this effect, and that it could be a potential new target for the treatment of heart disease.

“We believe that REDD1 manipulation could represent a new therapeutic strategy to restore insulin sensitivity in the diabetic heart and improve the health of heart disease patients,” Pfleger said.

The AHA is the largest U.S. nonprofit aiming to fight heart disease and stroke. The organization funds research with the potential to result in medical advancements. In July, the AHA awarded $20 million to five research teams working to prevent hypertension in underserved U.S. populations.

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