Targeting AMP Kinase in Myeloid Cells to Reduce Atherosclerosis

Subjects with diabetes have a 1.8 times greater risk of having a heart attack than subjects without diabetes. Although cardiovascular mortality has decreased by 30.8% in the last decade, it is still responsible for 1 in 3 deaths in the U.S. (1). In spite of targeting the common risk factors, there is still a residual burden for atherosclerotic cardiovascular disease (ASCVD) (2). As inflammatory processes are involved in every stage of atherosclerosis, targeting inflammation has become an attractive strategy for further reducing the incidence of ASCVD (3). AMP activated kinase (AMPK) is an enzyme that increases cellular ATP generation and diminishes ATP use for less critical processes (4). It regulates the transport of glucose, the synthesis of lipids and proteins, and the rate of fuel metabolism. It is also involved in regulating inflammation and oxidative and ER stress (5). AMPK may thus provide the link between nutrient, metabolic, and inflammatory stimuli. Dysregulation of AMPK may therefore play a role in the pathogenesis of diabetes, hypertension, and ASCVD. On the basis of the information cited above, activation of AMPK could prevent or treat these conditions. Although there is evidence that AMPK activation is atheroprotective, the specific mechanism responsible for this effect is unclear (6). To explore the hypothesis that the atheroprotective effect of AMPK is …