Lung Protein Seen as PH Biomarker and Likely Target for Treatments in Animal Study

Researchers suggest that a protein called ED-A+ Fn (ED-A domain containing fibronectin) could serve as a marker for pulmonary hypertension (PH), aiding in diagnosis and allowing better monitoring of treatment responses.

The study, “Lung tissue remodelling in MCT-induced pulmonary hypertension: a proposal for a novel scoring system and changes in extracellular matrix and fibrosis associated gene expression,” published in the journal Oncotarget, also suggested that the protein could be used for a targeted delivery of drugs, as antibodies against it are readily available.

Except pulmonary arterial hypertension (PAH), a PH subtype, few disease-specific treatment options available for people with PH. In an attempt to advance the development of new therapeutics, researchers at Jena University Hospital and Heinrich-Heine-University, both in Germany, studied a rat model of PH, focusing specifically on the remodeling of lung extracellular matrix — a meshwork of molecules that surround and support cells.

As a first step, the team constructed a scoring system for evaluating changes in the animals’ lung tissue, based on previously published data of changes occurring there. The total score was made up of subscores assessing changes in lung blood vessels and in different parts of the lung tissue itself.

Researchers found that rats with lung hypertension had a higher total score than healthy rats used as controls. Also, an analysis of gene activity in rat lung tissue revealed that nine genes were more active than normal. These genes were involved in fibrosis-related pathways and vascular remodelling.

Next, team members  investigated protein components of the extracellular matrix. They found that the protein ED-A+ Fn was present in higher levels in PH rats compared to controls. Although studies focusing on heart diseases have reported abnormalities in matrix molecules, few have focused on ED-A+ Fn, and the factor has never been studied in PH.

Since ED-A+ Fn was the only one of the examined proteins found in higher levels in the lungs, the team went on to analyze blood serum levels of the factor. They discovered higher serum levels of this protein in rats with PH than in control animals.

Researchers also noted that the factor’s levels in the blood correlated with the systolic pressure in the heart’s right ventricle — a measure of lung blood pressure. This suggested that the protein could be explored as a disease marker.

“We here present a novel histological scoring system to assess lung tissue remodelling in PH,” the researchers concluded. “The stable increased tissue deposition of ED-A+ Fn in PH as well as its dynamics in serum suggests a role as a promising novel biomarker and potential therapeutic target.”