Image by Andre E.X. Brown
Thrombus
The protein CIB1 may be a superior target for antithrombotic therapy, according to researchers.
The team found that CIB1 plays a role in thrombus development but not in initial clot formation.
“The Holy Grail of our field is to reduce unwanted thrombus formation without completely blocking other important platelet functions,” said study author Ulhas Naik, PhD, of Thomas Jefferson University in Philadelphia, Pennsylvania.
He and his colleagues believe targeting CIB1 may do just that.
In earlier work, the researchers showed that CIB1 was involved in thrombus formation. They found mice that lacked the CIB1 gene were less likely to form a thrombus.
That work also indicated that mice lacking the CIB1 were still able to form a platelet plug, suggesting this gene was involved only in the process of thrombus formation.
To investigate this possibility further and to demonstrate that the process was relevant to human physiology, Dr Naik and his colleagues conducted the current study.
The team described this work in PLOS ONE.
The researchers studied human platelets and probed the molecules that interacted with CIB1 at different time points after platelet activation.
The team found that CIB1 does not begin to bind and interact with platelet molecular machinery until after filopodia formation, which allows platelets to cross-link to one another and begin to form a plug.
The study also elucidated a number of molecules that CIB1 interacts with during outside-in signaling and thrombus formation.
“This work demonstrates that CIB1 could be a good antithrombotic drug target,” Dr Naik said. “If we block CIB1, it hampers thrombus formation without interfering with platelet plug formation. If developed further, blocking CIB1 could reduce the risk of heart attack and stroke without increasing the risk for excessive bleeding that is the trade-off of current medication.”
The next step for Dr Naik and his colleagues is screening for small-molecule compounds that would inhibit CIB1 and could be developed into new therapies.
