Thrombosis is the formation and coagulation of blood cells that lead to blood clots. The result of this in arteries supplying blood, oxygen and nutrients, to key organs can, therefore, be fatal. Now, researchers have highlighted a novel pathway in which a specific microRNA (also known as miRNA) can help to positively regulate arterial thrombosis.
Corresponding author Mark Feinburg and his group at the Brigham and Women’s Hospital published their work in The FASEB Journal at the end of last month.
miRNAs are short sequences of single-stranded DNA that have attracted significant attention in the last 10 years for their therapeutic potential. miRNAs contain a complementary sequence of DNA that binds to its messenger RNA (mRNA) partner, degrading that intermediate RNA and preventing the translation of its protein.
In arterial thrombosis, signalling through the NF-ĸB plays an important role in inflammation, endothelial cell (EC) activation, and subsequent EC dysfunction. The researchers had previously shown that a miRNA called miR-181b inhibits this inflammatory signalling pathway NF-ĸB induced when the researchers pre-treat GB cells with TNFα. At the time, the exact mechanism for how miR-181b’s anti-inflammatory effects worked remained unknown.
Advancing on this previous finding in the current study, they found that miR-181b reduces the formation of blood clots via the targeting of Card10--a protein involved in the NF-kB inflammatory pathway. When they injected miR-181b into a mouse model of carotid artery thrombosis they prevented blood clots by up to 73%, and preventing the eventual artery blockage by 1.6 fold.
“miRNAs are emerging as potential regulators of arterial thrombosis,” said Feinberg. “This study highlights the important link between inflammation in the vessel wall and thrombosis. Delivery of miR-181b or Card10 inhibition may constitute a new therapeutic approach to reduce arterial thrombosis.”