Potential therapy for venous thrombosis
doi:10.1038/nindia.2017.143 Published online 20 November 2017
Researchers have identified a novel mechanism that leads to formation of blood clots (thrombosis) in veins in response to low oxygen levels1, by homing in on key protein complexes that play vital roles in forming the clots.
Inhibiting the activity of one of these protein complexes prevents clot formation, making it a potential drug target for designing drugs to treat venous thrombosis.
At high altitudes, atmospheric oxygen levels plummet, exposing body tissues to low oxygen concentrations, and activating specific immune cells that trigger a cascade of molecular events. This results in inflammation, forming clots in the veins.
Biologists from India's Defence Research and Development Organisation, Armed Forces Medical College, Pune, and Command Hospital Chandigarh, studied how oxygen deficiency leads to the formation of blood clots in animals and patients.
Exposure to low oxygen levels triggered the release of hypoxia-inducible Factor (HIF)-1α, a protein complex that plays an integral role in the body's response to low oxygen concentrations. This protein complex, in turn, activated a gene known as NLRP3, which encodes NLRP3, a protein complex that eventually helps form venous clots.
Using a potential drug molecule that could inhibit the activities of HIF-1α and NLRP3, it was possible to stop the molecular processes that lead to venous blood clots.
This suggests that targeting the inflammation-causing protein complexes can effectively reduce such blood clots under low-oxygen conditions, says lead researcher Mohammad Zahid Ashraf.
1. Gupta, N. et al. Activation of NLRP3 inflammasome complex potentiates venous thrombosis in response to hypoxia. Proc. Natl. Acad. Sci. Unit. States. Am. 114, 4763-4768 (2017)