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Articles 1 - 3 of 3

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Endothelial Protein Kinase Map4k4 Promotes Vascular Inflammation And Atherosclerosis, Rachel J. Roth Flach, Athanasia Skoura, Anouch Matevossian, Laura V. Danai, Wei Zheng, Christian Cortes, Samit K. Bhattacharya, Myriam Aouadi, G. Nana Hagan, Joseph Yawe, Pranitha Vangala, Lorena Garcia Menendez, Marcus P. Cooper, Timothy P. Fitzgibbons, Leonard Buckbinder, Michael P. Czech Dec 2015

Endothelial Protein Kinase Map4k4 Promotes Vascular Inflammation And Atherosclerosis, Rachel J. Roth Flach, Athanasia Skoura, Anouch Matevossian, Laura V. Danai, Wei Zheng, Christian Cortes, Samit K. Bhattacharya, Myriam Aouadi, G. Nana Hagan, Joseph Yawe, Pranitha Vangala, Lorena Garcia Menendez, Marcus P. Cooper, Timothy P. Fitzgibbons, Leonard Buckbinder, Michael P. Czech

Program in Molecular Medicine Publications and Presentations

Signalling pathways that control endothelial cell (EC) permeability, leukocyte adhesion and inflammation are pivotal for atherosclerosis initiation and progression. Here we demonstrate that the Sterile-20-like mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), which has been implicated in inflammation, is abundantly expressed in ECs and in atherosclerotic plaques from mice and humans. On the basis of endothelial-specific MAP4K4 gene silencing and gene ablation experiments in Apoe(-/-) mice, we show that MAP4K4 in ECs markedly promotes Western diet-induced aortic macrophage accumulation and atherosclerotic plaque development. Treatment of Apoe(-/-) and Ldlr(-/-) mice with a selective small-molecule MAP4K4 inhibitor also markedly reduces atherosclerotic ...


Inducible Deletion Of Protein Kinase Map4k4 In Obese Mice Improves Insulin Sensitivity In Liver And Adipose Tissues, Laura V. Danai, Rachel J. Roth Flach, Joseph V Virbasius, Lorena Garcia Menendez, Dae Young Jung, Jong Hun Kim, Jason K. Kim, Michael P. Czech Jul 2015

Inducible Deletion Of Protein Kinase Map4k4 In Obese Mice Improves Insulin Sensitivity In Liver And Adipose Tissues, Laura V. Danai, Rachel J. Roth Flach, Joseph V Virbasius, Lorena Garcia Menendez, Dae Young Jung, Jong Hun Kim, Jason K. Kim, Michael P. Czech

Program in Molecular Medicine Publications and Presentations

Studies in vitro suggest that mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) attenuates insulin signaling, but confirmation in vivo is lacking since Map4k4 knockout is lethal during embryogenesis. We thus generated mice with floxed Map4k4 alleles and a tamoxifen-inducible Cre/ERT2 recombinase under the control of the ubiquitin C promoter to induce whole-body Map4k4 deletion after these animals reached maturity. Tamoxifen administration to these mice induced Map4k4 deletion in all tissues examined, causing decreased fasting blood glucose concentrations and enhanced insulin signaling to AKT in adipose tissue and liver but not in skeletal muscle. Surprisingly, however, mice generated with ...


Highly Selective In Vivo Labeling Of Subcutaneous White Adipocyte Precursors With Prx1-Cre, Joan Sanchez-Gurmaches, Wen-Yu Hsiao, David A. Guertin Apr 2015

Highly Selective In Vivo Labeling Of Subcutaneous White Adipocyte Precursors With Prx1-Cre, Joan Sanchez-Gurmaches, Wen-Yu Hsiao, David A. Guertin

Program in Molecular Medicine Publications and Presentations

The origins of individual fat depots are not well understood, and thus, the availability of tools useful for studying depot-specific adipose tissue development and function is limited. Cre drivers that selectively target only brown adipocyte, subcutaneous white adipocyte, or visceral white adipocyte precursors would have significant value because they could be used to selectively study individual depots without impacting the adipocyte precursors or intrinsic metabolic properties of the other depots. Here, we show that the majority of the precursor and mature subcutaneous white adipocytes in adult C57Bl/6 mice are labeled by Prx1-Cre. In sharp contrast, few to no brown ...