Investigators at the Fralin Biomedical Research Institute at Virginia Tech Carilion (VTC) have made a discovery in pulmonary arterial hypertension (PAH). They found patients with PAH have significantly reduced levels of bone morphogenetic protein 3 (BMP3) — a natural protective protein that regulates lung blood vessels.
The European Respiratory Journal published the group’s findings in the paper, “Paracrine Action of Bone Morphogenetic Protein 3 in Pulmonary Arterial Hypertension.” The authors said this is the first study to identify and analyze BMP3’s role in PAH.
Cells lining the walls of pulmonary blood vessels produce BMP3. In healthy lungs, the protein controls and protects blood vessel cells. In damaged lungs, low amounts of BMP3 can cause the blood vessels to thicken and narrow, restricting blood flow to the lungs.
“Pulmonary arterial hypertension remains a devastating disease with limited treatment options. Most current therapies focus on managing symptoms or slowing disease progression,” said senior author and associate professor Yassine Sassi, PhD, in a VTC news release. “What makes the discovery exciting is that it identifies a new therapeutic strategy aimed at restoring a natural protective mechanism that is lost during disease.”
In preclinical models, researchers used two different methods to increase the expression of BMP3: recombinant BMP3 protein and lung-targeted gene therapy. Both approaches significantly suppressed cellular changes, reduced disease severity and reversed key features of the disease, including damaged pulmonary blood vessels and reduced heart function, they said.
“This gives us two potential therapeutic paths forward: a biologic therapy and a gene-based approach, both designed to restore a natural protective signal that is lost during disease,” Dr. Sassi said.
In addition to using BMP3 as a therapeutic target, the team said its findings also suggest it could serve as a biomarker for monitoring disease. Additional studies are needed before the approach can be tested in patients, the authors said.
