Why is fibrinogen phosphorylated in heart disease?

The effects of increased fibrinogen phosphorylation on endothelial dysfunction and thrombus formation: Implications in atherosclerosis

Dr Kerrie Smith and her colleagues at the University of Leeds are studying why a protein called fibrinogen undergoes a chemical process called phosphorylation, and why high levels of phosphorylated fibrinogen are found in people with atherosclerosis, which is the build-up of fatty plaques in blood vessel walls. . Phosphorylation is the addition of a molecule called a phosphate group to another molecule. The function of a protein can be changed dramatically by phosphorylation. Fibrinogen is phosphorylated in liver cells and regulates the generation of blood clots needed to stop bleeding following injury and to repair the damaged tissue. But we don’t understand why fibrinogen is phosphorylated and how it aids blood clotting and tissue repair. People with inflammation-linked conditions, such as atherosclerosis, have very high levels of phosphorylated fibrinogen in their blood. But we don’t know what mechanisms control this and how it contributes to atherosclerosis. In this project, Dr Smith will uncover how the phosphorylation status of fibrinogen affects the behaviour of cells, the structure and formation of clots, and influences inflammation. Finally she will explore methods to reduce the amount of phosphorylated fibrinogen. This research could lead to the development of new drugs to treat inflammation and prevent it progressing to heart disease.