Although COVID-19 is known for its severe respiratory symptoms, the disease also has been associated with strokes in young people who had no known risk factors. A new UCLA-led study may help illuminate how the coronavirus interacts with certain cells in the brain.
Endothelial cells line the interior of blood vessels in organs, including the brain, heart and lungs. Previous research indicated that the coronavirus binds to endothelial cells in organs, but it was unknown whether or not that binding action was happening in the brain. UCLA researchers used a 3D-printed silicone model of blood vessels in the brain to mimic the forces generated by blood pushing through an artery that is abnormally narrowed — a condition called intracranial atherosclerosis. They showed that those forces act on the cells lining the artery and increase the production of a molecule called angiotensin-converting enzyme 2, or ACE2, which the coronavirus uses to enter cells on the surface of blood vessels. “The flow directly influences ACE2 expression,” says Jason Hinman, MD (FEL ’13), PhD, assistant professor of neurology. In addition to Hinman, the study’s authors are neurologists at the Geffen School of Medicine and scientists from UC San Francisco and the Veterans Health Administration.
To confirm if coronavirus bobbing along in the bloodstream could latch onto the ACE2 on the endothelial cells in the brain, researchers produced imitation “viruses” — fatty molecules studded with the spike proteins that coronavirus uses to bind to ACE2. After creating the new model, they confirmed that the particles did, indeed, interact with the cells lining the blood vessel, mostly in the regions of the brain with higher levels of ACE2. “Brain endothelial cells are susceptible to direct SARS-CoV-2 infection through flow-dependent expression of ACE2,” they concluded in the study.
The scientists also analyzed which genes were turned on in the endothelial cells after the coronavirus spike proteins bound to them. They found that the genes that were activated were a specific set of immune-response genes that are found in brain blood-vessel cells but not in endothelial cells from other organs of the body. This unique feature “may be helpful in identifying patients who have a higher risk for stroke,” Dr. Hinman says.
— Caroline Seydel
“Flow-mediated Susceptibility and Molecular Response of Cerebral Endothelia to SARS-CoV-2 Infection,” Stroke, January 2021