BME’s Merryman and collaborators find potential way to prevent rare lung disease

Research by Vanderbilt scientists suggests that it may be possible to prevent or even reverse pulmonary arterial hypertension (PAH), a rare, progressive disease characterized by narrowing of and high blood pressure in the small arteries of the lungs.

A key player in PAH is the proangiogenic cell (PAC), a cell produced by the bone marrow that normally promotes the growth of new blood vessels.

Last month in the journal Circulation Research the researchers reported finding PACs in the stiffened small blood vessels in the lungs of patients with PAH. In cell culture studies, they showed that PACs aggravate damage to the blood vessel lining, leading to scarring and narrowing.

W. David Merryman

They showed they could both prevent and reverse experimentally induced pulmonary hypertension in a mouse model by killing off the PACs, and also by giving a drug that blocked signaling through a serotonin receptor called 5-HT2B.

“We were quite surprised to find out that the driver of pulmonary hypertension appears to be a very small population of cells from the bone marrow,” said the paper’s corresponding author, W. David Merryman, professor of biomedical engineering, pharmacology, medicine and pediatrics. “It definitely changes the way we think about possible therapies for the disease.”

Approximately 500 to 1,000 cases of PAH are diagnosed each year in the United States. Untreated, the disease will eventually damage the heart.  It differs from other, more common forms of pulmonary hypertension, which usually involve  underlying diseases of the heart, lungs or other organs. Various medications can reduce blood pressure in the lungs and slow the course of the disease but doctors are not yet able to stop or reverse it. Additionally, similarity in symptoms to other diseases complicates diagnosis.

The findings by the Vanderbilt researchers suggest that serotonin signaling triggers the proliferation and homing of PACs. Thus targeting 5-HT2B could potentially lead to the first treatment capable of preventing and reversing PAH.

Nathanial Bloodworth, PhD, a student in Vanderbilt’s MD/PhD program, is the paper’s first author.

Vanderbilt faculty members who contributed to the study included Cynthia Clark, PhD, James West, PhD, Julie Bastarache, MD, Timothy Blackwell, MD, Harikrishna Tanjore, PhD, Evan Brittain, MD, MSCI, and Susan Majka, PhD.

The study was supported by National Institutes of Health grants HL135790, HL115103 and HL126280, and by the American Heart Association.

This story by Bill Snyder originally appeared in VUMC Reporter.