期刊
FASEB JOURNAL
卷 29, 期 2, 页码 597-610出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.14-262097
关键词
insulin resistance
资金
- U.S.National Institutes of Health (NIH) National Heart, Lung, and Blood Institute [R01HL107953, R01HL106063, R01HL105945, R01HL064793, R01HL061371]
- NIH National Institute on Aging Grant [1F31AG043318]
- Foundation Leducq Transatlantic Network of Excellence
- Spanish Ministry (Programa Nacional de Movilidad de Recursos Humanos del Plan Nacional de I-D+i)
- American Heart Association [12POST9780016]
- Howard Hughes Medical Institute International Student Research Fellowship
- Capes Foundation, Ministry of Education of Brazil, Brazil
Atherosclerosis is the major cause of death and disability in diabetic and obese subjects with insulin resistance. Akt2, a phosphoinositide-dependent serine-threonine protein kinase, is highly express in insulin-responsive tissues; however, its role during the progression of atherosclerosis remains unknown. Thus, we aimed to investigate the contribution of Akt2 during the progression of atherosclerosis. Wefound that germ-line Akt2 deficient mice develop similar atherosclerotic plaques as wild-type mice despite higher plasma lipids and glucose levels. It is noteworthy that transplantation of bonemarrow cells isolated from Akt2(-/-) mice to Ldlr(-/-) mice results in marked reduction of the progression of atherosclerosis compared with Ldlr(-/-) mice transplanted with wild-type bone marrow cells. In vitro studies indicate that Akt2 is required for macrophage migration in response to proatherogenic cytokines (monocyte chemotactic protein-1 and macrophage colony-stimulating factor). Moreover, Akt2(-/-) macrophages accumulate less cholesterol and have an alternative activated orM2-type phenotype when stimulated with proinflammatory cytokines. Together, these results provide evidence that macrophage Akt2 regulates migration, the inflammatory response and cholesterol metabolism and suggest that targeting Akt2 in macrophages might be beneficial for treating atherosclerosis.
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