The research team has created a mimetic of the last protein in the pathway, HSP20, which causes relaxation in the same way as the natural protein. This research, published May 8 in the online version of The FASEB Journal, is a major step in the development of a drug that promotes blood vessel relaxation.
The signaling pathway that causes relaxation in smooth muscle cells involves many different proteins, but the last step is the addition of a phosphate group, or phosphorylation, of the protein HSP20, which actually effects relaxation.
Other groups have developed molecules, such as the active ingredient in Viagra, that affect earlier steps in this pathway. But if a problem occurs in later steps, these compounds are ineffective.
"You've got all those signaling pathways, but, boom, you can bypass them by putting in a mimetic of the protein that's the effector molecule," said primary investigator Colleen Brophy, research professor of bioengineering at ASU, director of the Center for Protein and Peptide Pharmaceuticals in the Arizona Biodesign Institute, and chief of vascular surgery at the Carl T. Hayden Veterans Affairs Medical Center.
The HSP20 mimetic developed at ASU consists of a 13 amino acid stretch of the protein attached to a protein transduction domain, a peptide that allows the mimetic to enter cells. The HSP20 portion of the mimetic includes a phosphate group attached to the same amino acid as in the active version of natural HSP20.
Brophy and colleagues measured the contraction of thin rings of smooth muscle from the coronary arteries of pigs with a force transducer. They pre-contract
Contact: Linley Hall
Arizona State University