A step towards understanding why COVID-19 promotes stroke risk

A UCLA-led study may help explain how COVID-19 increases stroke risk. The scientists made the discovery by running a spiked fluid with a COVID-19-like protein through a 3-D printed model of the artery of a stroke patient.

Although COVID-19 was initially identified by its true respiratory symptoms, the virus has caused strokes in adolescents who did not have known risk factors. But little is known about how the virus increases the risk of stroke.

To learn more, UCLA researchers used a 3-D printed silicone model of blood vessels in the brain to report the forces generated by blood pushing through an abnormally narrowed artery, a setting called intracranial atherosclerosis. They showed how these forces work on the cells lining the arteries, and increase molecular production called angiotensin-converting enzyme 2, or ACE2, which the coronavirus uses to to enter cells on the surface of blood vessels.

“The flow directly affects the sensitivity of ACE2,” said Dr. Jason Hinman, assistant professor of neurology at UCLA’s David Geffen School of Medicine and senior author of the study.

In addition to Hinman, the study’s authors are neurologists at Geffen School of Medicine and scientists from UC San Francisco and the Veterans Health Administration. The paper was published in Stroke.

UCLA researchers created the model using data from CT scans of blood vessels in the human brain. They would then line the inner surface of the modules with endothelial cells, the type of cells that line human blood vessels. The models allowed the researchers to use the same forces that would work on real blood vessels during COVID-19 infection.

To test whether a coronavirus bobav in the bloodstream could capture the ACE2 on the endothelial cells in the brain, researchers reported “viruses” – strong molecules full of the spike proteins that coronavirus uses to bind to ACE2. Previous research has shown that the coronavirus binds to endothelial cells in other organs, but it was not known if this also occurred in the brain.

After creating the new model, researchers confirmed that the granules actually interacted with the cells lining the blood vessel, mostly in areas of the brain with higher levels. of ACE2.

“This finding could explain the increased incidence of strokes seen in COVID-19 infections,” Hinman said.

Another finding offered insights that may help identify people with COVID-19 who may be at higher risk for stroke. When the scientists analyzed which genes were turned on in the endothelial cells after attaching the spike coronavirus proteins to them, they found that the activated genes were a specific set of response genes -protection found in cerebral blood cells, but not in endothelial cells from other organs of the body.

“There is a brain-specific endothelial response to the virus that may be helpful in identifying patients at higher risk for stroke,” Hinman said.

The researchers plan to conduct follow-up studies using live coronavirus in the 3-D printed blood vessel model, which would confirm the results of the current study and clarify which COVID- patients 19 who may be at higher risk for stroke.