A research team at University of Michigan Health led by Ajay Tambralli, M.D., a clinical assistant professor in both adult and pediatric rheumatology, is investigating how metabolism – the process by which cells turn sugars, fats and proteins into energy – is used to make NETs.
They’re also using this knowledge to develop treatments based on metabolism to lower the propensity of neutrophils to make NETs in APS.
The team’s study found neutrophils from antiphospholipid syndrome patients use a metabolic process called glycolysis more aggressively than neutrophils from healthy people.
Glycolysis converts sugars into energy and generates by-products used for different purposes in the cell.
The authors found that one such by-product called glucose-6-phosphate feeds into another metabolic process known as the pentose phosphate pathway.
The pentose phosphate pathway then arms the neutrophils to make NETs.
“When we disrupted either glycolysis or the pentose phosphate pathway, neutrophils made fewer NETs. Fewer NETs meant smaller blood clots in our model systems,” said Tambralli.
Promisingly, they also found that this strategy didn’t increase bleeding.
Though more research is needed, the goal is to bring such treatments to patients with antiphospholipid syndrome and, potentially, other diseases where NETs cause blood clotting.
