Researchers at the University of California San Diego announced on Mar. 10 that they have discovered how a single protein, known as protease-activated receptor-1 (PAR1), can trigger two opposite responses in blood vessels—one that is inflammatory and another that is protective. The study highlights PAR1's critical role in maintaining the structural integrity of blood vessels.
This finding is significant because it could lead to new treatments for diseases characterized by vascular inflammation and leakage, such as sepsis, heart attack, and stroke. Understanding how PAR1 switches between healing and harmful signaling pathways may help scientists develop therapies that target only the beneficial effects.
PAR1 is located on the surface of cells lining blood vessels and becomes active when chemically cut by one of two enzymes. Depending on which enzyme activates it, PAR1 can either cause inflammation and leakage or counteract inflammation with a protective response. Until now, researchers did not understand how a single molecule could be responsible for such opposing actions.
"This opens the door to therapies that could harness the protective response of PAR1 without potentially triggering the opposite response," said Irina Kufareva, PhD, professor at the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences.
The discovery provides new insight into vascular biology and suggests future research may focus on developing drugs that selectively activate only the protective pathway of PAR1.
