Abstract We052: Angiotensin-converting enzyme (ACE): A new role to regulate β-oxidation in monocytic cells

Abstract

The metabolic failure of macrophages to adequately process lipid, and the deleterious effects of ingested lipid on macrophage behavior, is central to the etiology of atherosclerosis. As angiotensin-converting enzyme (ACE) has major effects on myeloid cell metabolism, we examined the role of macrophage ACE in a mouse model of atherosclerosis. Animals with increased macrophage ACE expression (ACE 10/10 mice) have a marked reduction in atherosclerosis vs. WT mice. Macrophages from both the aorta and peritoneum of ACE 10/10 express increased PPARα and higher levels of effector molecules downstream of PPARα. These macrophages have increased basal and maximal oxygen consumption compared to WT macrophages. When exposed to lipid in vitro, ACE 10/10 macrophages ingest more fatty acid than WT and have increased efferocytosis. ACE 10/10 macrophages metabolize via β oxidation far more fatty acid than WT cells as determined using 13C isotope tracing. In part by increasing PPARα, ACE boosts myeloid metabolic function under pathophysiologic lipid stress, addressing a key myeloid failure in atherosclerosis.