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Loss of 2 Akt (Protein Kinase B) Isoforms in Hematopoietic Cells Diminished
Monocyte and Macrophage Survival and Reduces Atherosclerosis in Ldl
Receptor-Null Mice.
Authors Babaev VR, Ding L, Zhang Y, May JM, Ramsey SA, Vickers KC, Linton MF
Submitted By Submitted Externally on 1/25/2019
Status Published
Journal Arteriosclerosis, thrombosis, and vascular biology
Year 2019
Date Published 2/1/2019
Volume : Pages 39 : 156 - 169
PubMed Reference 30567482
Abstract Objective- Macrophages express 3 Akt (protein kinase B) isoforms, Akt1, Akt2,
and Akt3, which display isoform-specific functions but may be redundant in terms
of Akt survival signaling. We hypothesize that loss of 2 Akt isoforms in
macrophages will suppress their ability to survive and modulate the development
of atherosclerosis. Approach and Results- To test this hypothesis, we
reconstituted male Ldlr-/- mice with double Akt2/Akt3 knockout hematopoietic
cells expressing only the Akt1 isoform (Akt1only). There were no differences in
body weight and plasma lipid levels between the groups after 8 weeks of the
Western diet; however, Akt1only? Ldlr-/- mice developed smaller (57.6%
reduction) atherosclerotic lesions with more apoptotic macrophages than control
mice transplanted with WT (wild type) cells. Next, male and female Ldlr-/- mice
were reconstituted with double Akt1/Akt2 knockout hematopoietic cells expressing
the Akt3 isoform (Akt3only). Female and male Akt3only? Ldlr-/- recipients had
significantly smaller (61% and 41%, respectively) lesions than the control WT?
Ldlr-/- mice. Loss of 2 Akt isoforms in hematopoietic cells resulted in markedly
diminished levels of white blood cells, B cells, and monocytes and compromised
viability of monocytes and peritoneal macrophages compared with WT cells. In
response to lipopolysaccharides, macrophages with a single Akt isoform expressed
low levels of inflammatory cytokines; however, Akt1only macrophages were
distinct in expressing high levels of antiapoptotic Il10 compared with WT and
Akt3only cells. Conclusions- Loss of 2 Akt isoforms in hematopoietic cells,
preserving only a single Akt1 or Akt3 isoform, markedly compromises monocyte and
macrophage viability and diminishes early atherosclerosis in Ldlr-/- mice.


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