A protein derived from the salivary glands of ticks homes in on immune molecules called chemokines that promote atherosclerosis, a new study shows (Bioconj. Chem.2020, DOI: 10.1021/acs.bioconjchem.0c00095). By attaching a fluorescent marker to a synthetic version of the protein, called Evasin-3, researchers were able to visualize inflammation on tissue inside arteries.
“I was very intrigued that we could use nature for imaging human diseases,” says study leader Ingrid Dijkgraaf, a biochemist at the Cardiovascular Research Institute of Maastricht University.
In atherosclerosis, fatty acids glom on to the artery wall, activating a rush of immune response, including chemokines. Imaging techniques such as ultrasound or positron emission tomography (PET) can visualize the fatty plaques themselves, but not the inflammatory processes that make them dangerous. That capability would help clinicians differentiate between disease-causing plaques, which can rupture and cause a blood clot, and those that accumulate normally in the course of aging, Dijkgraaf explains.
The researchers conscripted Evasin-3 for the job because this tick protein naturally binds to chemokines to suppress the host immune system. They chemically synthesized a version of the protein in which a carbohydrate group was replaced with a green fluorescent marker. When they delivered an inflammation-triggering lipid to an intact section of a mouse carotid artery along with the fluorescent tick protein, the tissue turned green, lighting up the accumulation of chemokines on the scene. “If there’s a high expression of these chemokines, we see our protein accumulating there,” Dijkgraaf says.
The researchers next plan to test the approach in a mouse model of atherosclerosis. They also plan to replace the fluorescent marker, which cannot be visualized deep in tissue, with a radioactive label that can be used for PET imaging in humans.