Tricking immune cells to repair fatty deposits

Molecular mechanisms and therapeutic potential of Activating Transcription Factor -1 (ATF-1) in gene regulation in atheroprotective M-hem plaque macrophages

In this Senior Clinical Research Fellowship, Dr Boyle will test whether a special type of immune cell, called a macrophage, can help to repair inflamed blood vessels in atherosclerosis, the condition that causes coronary heart disease. He will test if a commonly used antidiabetic medicine, metformin, could boost the development of these repairing macrophages. Coronary heart disease occurs because of the build-up of abnormal fatty deposits in the blood vessels supplying the heart, a process called atherosclerosis. The fatty deposits trigger macrophages to damage the vessel wall. Dr Boyle has discovered that bleeds within the fatty deposits lead to the development of a new type of macrophage that instead seems to repair the fatty deposits. He has identified a master regulator gene, which, when activated, could trick these white cells into repairing fatty deposits of their own accord. In this fellowship, Dr Boyle will explore the pathways that activate this master regulator gene further and will test whether an important and safe antidiabetic medicine activates this protective switch, which would mean that it might directly protect heart vessels from fatty build up.