Help for the Heart Surgeon

During standard coronary bypass surgery the surgeon removes veins from the patient’s legs. Those veins are then used to bypass blocked arteries around the patient’s heart.

The transplanted vein often clenches when it is removed from the body. Called vasospasm, this clenching is one of the primary reasons the procedure can fail. Bleeding in the brain from a ruptured aneurysm can also cause severe spasm of nearby blood vessels, which leads to stroke.

Blood vessels and other organs contain lots of smooth muscle cells. A complex signaling pathway controls relaxation in smooth muscle cells, but researchers at Arizona State University have discovered how to bypass it.

Colleen Brophy and her colleagues at the Biodesign Institute at Arizona State University found that an enzyme activates the last protein in this pathway. The protein is called HSP20. The ASU team created a mimetic of HSP20 as a potential drug to prevent vasospasm. The mimetic imitates the natural protein by causing the smooth muscle cells to relax in the same way.

Brophy is a research professor of bioengineering and director of the Center for Protein and Peptide Pharmaceuticals. She also is chief of vascular surgery at the Carl T. Hayden Veterans Affairs Medical Center in Phoenix.

She says that most drugs are small molecules that can be made chemically. A protein is huge in comparison. Proteins are difficult to get inside a cell. They also may require a biological system for production. However, a protein-based drug is more efficient and highly targeted.

“We bypass all those signaling pathways by putting in a mimetic of the protein that’s the key molecule,” Brophy explains.

To create the HSP20 mimetic, the ASU team used computer models to look at potential improvements to the protein. The scientists made promising mimetics in the laboratory. The new proteins were then tested to see if they would cause relaxation in strips of blood vessel. Testing in laboratory animals was next.

The next step will be to take a HSP20 mimetic into stage one clinical trials. Stage one trials test the safety and effectiveness of new drugs or procedures on human patients. The overall goal of the ASU research is to create protein-based pharmaceuticals to treat a variety of diseases.

“I’m interested in approaching science from a bedside to bench and back to bedside approach,” Brophy says. —Linley Erin Hall