Inhibition of miR-33 Increases Mitochondrial Biogenesis and Improves Mitochondrial Function

Macrophages play a critical role throughout atherogenesis, from the initiating events leading to plaque formation to the development of plaque instability and thrombosis. Uptake of modified forms of low-density lipoprotein by macrophages within the arterial wall leads to their transition into arterial foam cells and the development of atherosclerotic plaques. In addition, as plaques mature and macrophage-derived foam cells continue to accumulate lipids, many undergo apoptosis, and the inability of other macrophages to efficiently remove apoptotic cells within atherosclerotic plaques leads to the formation of the necrotic core, a hallmark of plaque instability. Finally, macrophages produce and secrete several matrix metalloproteinases that can promote degradation of the fibrous cap and increase likelihood of plaque rupture.