Study Highlights Inhibitory Role of MicroRNA in Preventing Arterial Thrombosis

MicroRNA inhibition of a thrombin-related protein was found to reduce the formation of blood clots in the arteries of a mouse model with photochemical injury-induced arterial thrombosis.

Thrombin is an inflammatory mediator that can induce NF-kappaB–mediated endothelial cell (EC) activation and dysfunction, which contribute to the pathogenesis of arterial thrombosis. Previous studies carried out by investigators at Harvard Medical School (Boston, MA, USA) showed that the microRNA miR-181b inhibited downstream NF-kappaB signaling in response to TNF (tumor necrosis factor)-alpha.

MicroRNAs are a class of about 20 nucleotides-long RNA fragments that block gene expression by attaching to molecules of messenger RNA in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA. With their capacity to fine-tune protein expression via sequence-specific interactions, miRNAs help regulate cell maintenance and differentiation.

In a follow-up study using mouse models of carotid artery thrombosis, the investigators demonstrated that miR-181b uniquely inhibited upstream NF-kappaB signaling in response to thrombin. They reported in the June 13, 2016, online edition of The FASEB Journal that the delivery of miR-181b reduced the formation of blood clots by 73% in carotid arteries and prolonged the time to artery blockage by 1.6 fold.

Mechanistically, miR-181b targeted and suppressed an inflammatory factor, the adaptor protein Card10 (caspase recruitment domain family member 10). Direct blocking of Card10 activity with a small inhibitory RNA (siRNA) gave the same results as those seen when Card10 was inhibited by miR-181b.

"miRNAs are emerging as potential regulators of arterial thrombosis," said senior author Mark Feinberg, associate professor of Medicine at Harvard Medical. "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."

Related Links:
Harvard Medical School