Defining the specific roles of a group of proteins in atherosclerosis

Defining the individual and integrated roles of inflammatory chemokine receptors (iCCRs) in atherosclerosis

Atherosclerosis is the main cause of heart attacks and strokes. It is a disease where arteries become clogged with fatty deposits called plaques. Inflammation of artery walls is a key feature of atherosclerosis. During plaque formation, cells of the artery wall release small proteins called chemokines. Chemokines bind to chemokine receptors on the surface of immune cells and guide them to the site of tissue damage, causing inflammation. However, we have a limited understanding of precisely how chemokine receptors coordinate this inflammatory response, because there are numerous chemokines that have overlapping functions and bind to more than one receptor. Therefore, it is difficult to determine the role of individual chemokine receptors and design effective anti-inflammatory drugs that block their interactions with chemokines. To overcome this problem, researchers at the University of Glasgow have generated genetically-engineered mice in which the genes for a selection of chemokine receptors have been switched off. They will also create genetically-engineered mice where the gene for each chemokine receptor can be switched on individually, or in combination with other receptors. The researchers, led by Dr Pasquale Maffia, aim to discover if targeting an individual or specific combination of chemokine receptors could be an effective approach for preventing the inflammation that occurs in atherosclerosis.