What makes blood vessels leaky: new insights into the treatment of sepsis

The occurrence of sepsis is due to the body's efforts to fight infection, and the over-activated immune system damages the patient's own tissues as collateral damage

Researchers at the University of California San Diego School of Medicine are working to better understand how the body controls vascular permeability and how they might intervene to restore vascular integrity in the event of sepsis, trauma, or other conditions

The research team recently discovered that a protein called HSP27 plays a role in regulating vascular leakage

This research, published in the journal Science Signaling on August 31, 2021, provides new potential targets for the development of drugs that support the vascular barrier and prevent fluid loss

"This new information will help the root of the leaky blood vessels in our home, instead of taking a broad stroke approach, there may be many non-target effects," said senior author JoAnn Trejo

For example, the vascular barrier must be dynamic and have sufficient permeability to allow immune cells to squeeze out and reach the site of infection, but not leak so much that it is life-threatening

Tejo has long been studying G protein-coupled receptors (GPCRs), which are proteins that are embedded in the cell membrane of the whole body.

In their latest study, the research team found that during inflammation, GPCRs tell an enzyme called kinase to add a chemical (phosphate) tag to HSP27

One challenge in targeting GPCRs to treat diseases is that most GPCRs are major regulatory factors that affect several different cellular functions

"Obviously, you can develop different molecules that can bind to receptors and'bias' them-making them signal certain pathways in a very specific way, but not others," Trejo said

The team plans to explore additional cell signaling pathways to help blood vessels build the ability to resist damage and inflammation

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