Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Cell Metab 2007 Dec;6(6):446-57
Date
12/07/2007Pubmed ID
18054314Pubmed Central ID
PMC3621848DOI
10.1016/j.cmet.2007.10.007Scopus ID
2-s2.0-36448943901 (requires institutional sign-in at Scopus site) 266 CitationsAbstract
The Akt signaling pathway controls several cellular functions in the cardiovascular system; however, its role in atherogenesis is unknown. Here, we show that the genetic ablation of Akt1 on an apolipoprotein E knockout background (ApoE(-/-)Akt1(-/-)) increases aortic lesion expansion and promotes coronary atherosclerosis. Mechanistically, lesion formation is due to the enhanced expression of proinflammatory genes and endothelial cell and macrophage apoptosis. Bone marrow transfer experiments showing that macrophages from ApoE(-/-)Akt1(-/-) donors were not sufficient to worsen atherogenesis when transferred to ApoE(-/-) recipients suggest that lesion expansion in the ApoE(-/-)Akt1(-/-) strain might be of vascular origin. In the vessel wall, the loss of Akt1 increases inflammatory mediators and reduces eNOS phosphorylation, suggesting that Akt1 exerts vascular protection against atherogenesis. The presence of coronary lesions in ApoE(-/-)Akt1(-/-) mice provides a new model for studying the mechanisms of acute coronary syndrome in humans.
Author List
Fernández-Hernando C, Ackah E, Yu J, Suárez Y, Murata T, Iwakiri Y, Prendergast J, Miao RQ, Birnbaum MJ, Sessa WCMESH terms used to index this publication - Major topics in bold
Acute Coronary SyndromeAnimals
Apolipoproteins E
Apoptosis
Atherosclerosis
Bone Marrow Transplantation
Coronary Occlusion
Disease Models, Animal
Endothelial Cells
Female
Humans
Inflammation Mediators
Macrophages
Male
Mice
Mice, Knockout
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Proto-Oncogene Proteins c-akt
