Role of overlooked protein redefines our understanding of blood clots

Tuesday, September 02, 2014
Professor Heyu Ni and Yiming Wang
Professor Heyu Ni and Yiming Wang

For years it’s been overlooked when preparing blood products for patients. But researchers from the University of Toronto have discovered that the role of a particular protein may be the key to treating heart attack and stroke patients with bleeding disorders.

Professor Heyu Ni and PhD candidate Yiming Wang from the Department of Laboratory Medicine and Pathobiology (LMP) have revealed that a protein called fibronectin plays an essential role in properly forming blood clots. The team published their findings in the Journal of Clinical Investigation on September 2, 2014. 

In the past, scientists and clinicians believed that platelets were the “first wave” to stop bleeding.

However, by using high resolution imaging, Prof. Ni and Wang have shown that when a blood vessel’s wall is damaged, fibronectin quickly deposits onto the injured vessel wall even before platelets. Fibronectin is the glue that holds the initial repair in place and blood platelets arrive later to create a solid blood clot.

“This protein has been linked to blood clots for a long time, but nobody could make the connection to hemostasis, a process to stop bleeding. We’ve found that fibronectin arrives before platelets and is a key player in hemostasis,” said Prof. Ni.

But what prevents a blood clot from growing uncontrollably? The team believes that fibronectin is finely tuned to form the clot to the required size and then to switch off.

The implications for this research are wide-ranging. Heart disease and stroke are two of the three leading causes of death in Canada. Scientific advances made in this area are essential for treating an estimated 70,000 heart attacks and 50,000 strokes each year.

Patients who have a heart attack or stroke, or undergo certain types of surgery, are prescribed high doses of blood thinners to prevent dangerous blood clots from forming. But some patients are faced with a dilemma if they have a higher risk of bleeding. While the blood thinners prevent more clots from forming, they can also cause uncontrollable bleeding and death.

Prof. Ni’s research suggests that these at-risk patients could benefit from a transfusion of plasma fibronectin to help heal blood vessels without causing another blockage in the blood vessel.

“When we didn’t know about the role of fibronectin, we would discard this protein when developing some of the blood products,” explained Prof. Ni. “Now we know that fibronectin is important and we could take that unused protein and use it for patients who have bleeding problems following treatment of blood thinners.”

As a PhD candidate, Wang is excited to have worked on this project. He came to LMP from China where he was a medical student with an interest in cardiology.

“In cardiology you use a catheter to break up a blood clot. But I was interested in how to prevent heart attacks in the first place,” said Wang. “As an international student, it was challenging because I wasn’t eligible for many awards. But LMP was really supportive and helped me to get funding for the last four years from Canadian Blood Services.”

He’s also found support from Prof. Ni, “At first, I felt like my field was really narrow, but with the help of Dr. Ni and other people in the Ni lab, my research has completely opened up. Dr. Ni supported me to attend conferences around the world and I have even more ideas—it’s endless.”

The team now plans to study how fibronectin plays a role in another type of blood clot called deep vein thrombosis.

Ni said, “It’s such a sophisticated protein. We’re looking forward to seeing how we can use it to treat patients and what role it plays in other cardiovascular diseases.”