The discovery of a molecular factor that triggers blood clots in lung arteries may explain why chronic thromboembolic pulmonary hypertension (CTEPH) often occurs in patients without traditional clotting risk factors, according to a study.
Researchers think the factor, called activated TAFI, could be used to identify those with CTEPH. And targeting the molecule could be a way to develop new treatments for the condition, they added. CTEPH is a form of pulmonary hypertension that, as its name suggests, is caused by clotting.
The study, “Activated TAFI Promotes the Development of Chronic Thromboembolic Pulmonary Hypertension: A Possible Novel Therapeutic Target,” was published in the journal Circulation Research.
CTEPH has long been considered a complication of a lung embolism, or blood clot. But research shows that many people develop the condition without previous episodes of clots in lungs or veins.
Since lung arteries are constantly exposed to microscopic clots, researchers at Tohoku University Graduate School of Medicine in Japan hypothesized that a molecular factor might cause tiny aggregations of blood cells to create larger clots.
They discovered in earlier research that CTEPH patients had higher blood levels of a factor called TAFI than pulmonary arterial hypertension patients, or healthy people. They also found that the higher the level of the activated form of the protein, the longer it took for a clot to dissolve.
To see if the factor was directly involved in the mechanisms leading to CTEPH, the team studied several mouse models of the condition. They discovered that levels of activated TAFI rise as oxygen levels fall in lung arteries. Activation of the factor triggered inflammation and changes in blood vessels that further promoted the formation of clots, they said.
“In conclusion, TAFI is a crucial molecule in the development of PH [pulmonary hypertension] and thrombus formation in pulmonary arteries, and is useful as a novel biomarker and a therapeutic target of CTEPH,” the team wrote.
Importantly, the team was able to minimize pulmonary hypertension in mice by using drugs that block TAFI. The therapies included a class of drugs called PPAR-alpha agonists that doctors already use to lower blood fats. Building on the TAFI blocking approach could be a way to develop more CTEPH drugs, the team said.