Prolargin Shows Early Promise as PAH Biomarker

Forest Ray PhD avatar

by Forest Ray PhD |

Share this article:

Share article via email
prolargin results

The prolargin protein may serve as a biomarker for pulmonary arterial hypertension (PAH), allowing for earlier diagnosis and differentiating among different types of pulmonary hypertension (PH), according to a recent study.

The study, “Plasma proteoglycan prolargin in diagnosis and differentiation of pulmonary arterial hypertension,” was published in the journal ESC Heart Failure.

PAH can cause right heart failure, but non-specific symptoms such as shortness of breath (dyspnea) and fatigue can complicate obtaining a timely diagnosis. In fact, such symptoms can delay diagnosis by two years or more.

A screening method to differentiate PAH from other conditions that cause symptoms such as dyspnea, as well as distinguish PH subtypes, could reduce this time and improve patient outcomes.

That need drove a team of scientists from Lund University, in Sweden, to examine a class of proteins called proteoglycans for their ability to serve as such a biomarker.

Proteoglycans affect the development and signaling capability of the extracellular matrix (ECM), the network of molecules that surrounds and supports cells. Changes in the ECM occur over the course of PAH and can drive disease progression.

In PAH, an inflammatory pattern involving elevated levels of certain proteoglycans has been associated with worse clinical outcomes.

The Lund team identified 152 patients, ages 18 and older, who were experiencing dyspnea. They were examined at diagnosis with right heart catheterization, a test to evaluate cardiac health.

Patients had PAH, chronic thromboembolic pulmonary hypertension (CTEPH), PH due to heart failure with preserved or reduced ejection fraction, or heart failure with preserved or reduced ejection fraction but without PH. Twenty healthy controls were included. Notably, ejection fraction compares the amount of blood in the heart to the amount of blood pumped out to indicate how well the heart is pumping blood.

Results showed that the greatest difference in protein levels was that of prolargin, a proteoglycan associated with the ECM. Prolargin levels in the blood were higher in PAH than in controls, but lower compared with the other groups.

PAH patients also showed higher levels of IL-17D (a molecule implicated in inflammation) compared to controls, but lower levels relative to the other groups. Levels of the proteoglycan decorin were higher in all PH groups compared to the controls.

Prolargin is found in the skin, lungs, heart, and other tissues, where it helps cells remain fixed to the ECM and holds the complement system — a branch of the immune system that amplifies the inflammatory effects of other immune cells — in check. Excessive complement system activation can cause dangerous immune reactions.

Because of the role that inflammation plays in the development and progression of PAH, the investigators said that inflammation may drive the higher levels of prolargin seen in this study.

Whether the smaller rise in prolargin in PAH relative to the other disease groups indicates less inflammation in PAH, or if it involves different biological processes, remains unknown.

Still, the results suggest that prolargin may prove a useful addition to current diagnostic tools.

Prolargin’s ability to distinguish PAH, the researchers wrote, “warrants further investigation and could be enhanced by prolargin being a part of a multi‐marker panel.”

“Importantly,” they concluded, “larger studies using matched controls are needed to evaluate the definite use of prolargin as a marker for PAH in a broader population, also involving diseases other than PH, which exhibit dyspnoea.”

A Conversation With Rare Disease Advocates