Abstract 283: Role of AMP-Activated Protein Kinase α1 in Atherosclerosis
AMP-activated protein kinase (AMPK) is a key regulator of cellular energy and has cardiovascular protective effects. The catalytic subunit of AMPK consists of α1 and α2 isoforms and AMPKα1 is highly expressed in vascular cells and macrophages. To investigate the potential role of AMPKα1 in atherosclerotic processes, we crossed AMPKα1 deficient (AMPKα1-/-) mice with atherogenic ApoE deficient (ApoE-/-) mice. ApoE-/-/AMPKα1-/- mice and control ApoE-/- mice were fed a Western diet for 10 weeks. Deficiency of AMPKα1caused a lessened lesion area and decreased monocyte/macrophage infiltration of the lesions without significant lipid profile changes. Further, hematopoietic deficiency of AMPKα1 by bone marrow transplantation resulted in less atherosclerotic lesions, suggesting that AMPKα1 in bone marrow-derived cells, possibly macrophages, plays an important role in atherosclerosis development. Indeed, AMPKα1 deletion dramatically increased monocyte/macrophage apoptosis and cell death. Monocyte to macrophage differentiation was also impaired in AMPKα1-/- mice. The impaired monocyte differentiation and increased macrophage death were associated with the inhibition of autophagy induced by AMPKα1 deficiency. Taken together, our results reveal a novel role of AMPKα1 in controlling differentiation and survival of monocytic cells, and progression of atherosclerosis.
Author Disclosures: M. Zhang: None. H. Zhu: None. Y. Ding: None. C. Moriasi: None. Z. Liu: None. M. Zou: None.
- © 2014 by American Heart Association, Inc.