BNP hormone may actively promote blood clot formation, study finds

A hormone found in the blood and long viewed as a biological "check engine light" may do more than signal cardiovascular distress, according to researchers with the Texas A&M University Irma Lerma Rangel College of Pharmacy at Texas A&M Health.

Doctors regularly test for elevated levels of a hormone called B-type natriuretic peptide, or BNP, and its related protein fragments as indicators that the heart muscle is under stress from heart failure or another cardiovascular disease. As the leading cause of death in the United States, heart disease claims a life nearly every 34 seconds, with heart failure-a progressive condition where the heart struggles to pump enough blood throughout the body-a major driver of these fatalities.

Led by Dr. Zhenyu Li, a professor of pharmaceutical sciences, the research team discovered that high levels of BNP actively drive blood platelets to clump together, directly accelerating the formation of blood clots and blockages.

What makes this discovery so surprising?

Medical professionals have generally viewed BNP as a messenger of cardiac stress, helping them diagnose cardiovascular disease, according to Harvard Health. However, Li's lab suspected there was more to the story.

"We thought that BNP might not only act as a passive marker but actively contributes to the pathogenesis and progression of cardiovascular disease," Li said.

The recently published study demonstrates that BNP promotes platelet activation and thrombus formation, which can lead to serious health issues such as heart attacks. The breakthrough represents decades of careful investigation, Li noted.

"It has been an ongoing, gradual progression-not a sudden breakthrough, but a logical continuation of our research over the past two decades," he said.

How does BNP contribute to clotting?

When blood vessels are damaged by trauma like cuts or scrapes, platelets rush to the site and clump together to stop the bleeding. However, when platelets become hyperactive, they form clots inside the blood vessels-even without an external injury-that block blood flow, preventing red blood cells from carrying out their main job of delivering oxygen to tissues and organs, according to the American Society of Hematology.

Li's team uncovered a molecular chain reaction that can lead to this hyperactive behavior. In this reaction, the BNP hormone binds directly to a specialized surface receptor on platelets known as natriuretic peptide receptor-A, or NPRA.

"It was previously unknown whether platelets even expressed this receptor," Li explained. "We are the first team to investigate whether BNP directly activates platelets through the NPRA receptor."

When BNP binds to NPRA, it elevates a signaling molecule called cyclic guanosine monophosphate (cGMP) inside platelets. This spark triggers a suite of pro-clotting behaviors-boosting platelet aggregation and clot growth. In studies of vascular injury and pulmonary embolism, elevated BNP markedly accelerated clot formation.

Conversely, when NPRA receptors were absent or blocked, BNP lost its ability to raise cGMP or activate platelets, preventing abnormal clot formation and maintaining healthy blood flow. The team confirmed these findings in blood samples from people with heart rhythm disorders, showing that circulating BNP levels directly correlate with platelet activity in these patients. Simply put, BNP's ability to drive blood clotting depends on its interaction with these specific NPRA receptors on platelets.

"Knocking out the NPRA gene protected against these complications, proving the clotting process is mediated by the NPRA receptor," Li said.

What does this mean for patients?

The discovery provides a biological explanation for why patients with high BNP levels face significantly elevated risks of severe cardiovascular events like heart attacks and pulmonary embolisms. More importantly, this new understanding could unlock the potential for researchers to develop safer, more specific therapies.

Standard antiplatelet medications suppress blood clotting globally throughout the body, carrying a persistent risk of dangerous internal bleeding. By focusing on the BNP–NPRA pathway, pharmaceutical developers can design targeted therapies that prevent BNP-driven clot formation without impairing the body's general ability to heal injuries, Li said.

Until these targeted therapies are available, however, Li's research suggests physicians may need to closely monitor patients with elevated BNP and consider whether antiplatelet therapy could help prevent or reduce the risk of blood clots and related complications.

What comes next?

Future studies will involve selectively removing NPRA from platelets or other specific cell types to help determine if platelet NPRA is the primary driver of BNP-induced thrombosis.

"Platelets appear to be major contributors, and to confirm this further, we need to develop tissue-specific models," Li said.

The collaborative study was co-led by Zhenyu Li, Fadi T. Khasawneh, Yinan Wei, and Fatima Z. Alshbool, faculty members at the Rangel College of Pharmacy. Yan Zhang and Guoying Zhang, also affiliated with the college, contributed as co-first authors.

The team is collaborating with Dr. Wenshe Liu, Regents Professor and Harry E. Bovay, Jr. Chair in Chemistry at the Texas A&M College of Arts and Sciences, to identify small-molecule inhibitors capable of blocking the BNP–NPRA interaction. Promising compounds will undergo further testing to determine whether they can prevent BNP-induced platelet activation and thrombosis.

Unlike current antiplatelet drugs that can disrupt overall platelet activity, homing in on this specific pathway could lay the groundwork for targeted therapies that block life-threatening blood clots while also preserving normal, healthy clotting.

"Because patients with high BNP levels face the greatest risk, targeting this pathway opens new opportunities to reduce thrombotic complications while minimizing standard side effects like severe bleeding," Li said.