Uncoupling protein 2-mediated thermogenesis in vulnerable atherosclerotic plaques.

Timely detection of vulnerable atherosclerotic plaques is of the utmost importance to prevent acute clinical events, such as unstable angina, myocardial infarction and sudden death. Advanced plaques show a dense infiltration of macrophages, of which a subpopulation strongly expresses uncoupling protein 2 (UCP2). This protein uncouples adenosine triphosphate (ATP) production from mitochondrial respiration and thereby converts the loss of potential energy in heat production. In early atherosclerotic lesions, UCP2 seems to fulfil an atheroprotective effect by reducing reactive oxygen species (ROS) production and/or by inhibiting monocyte recruitment. Because the amount of macrophages in these lesions is limited, effects on plaque temperature cannot be detected. As the macrophage content of the plaque increases and the plaque progresses toward an unstable phenotype, ROS production is overwhelming, and possibly cannot be counteracted by the antioxidant properties of UCP2. However, the increasing number of UCP2-positive macrophages inside advanced plaques correlates with increased plaque temperature. This thermogenic effect can be detected by intravascular thermography and may be indicative of rupture-prone regions. Thus, UCP2 expression in macrophages in advanced plaques can be considered a biochemical link between plaque temperature and vulnerability.