Mechanism and role of high density lipoprotein-induced activation of AMP-activated protein kinase in endothelial cells

Takao Kimura, Hideaki Tomura, Koichi Sato, Masaaki Ito, Isao Matsuoka, Doon Soon Im, Atsushi Kuwabara, Chihiro Mogi, Hiroshi Itoh, Hitoshi Kurose, Masami Murakami, Fumikazu Okajima

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Abstract

The upstream signaling pathway leading to the activation of AMP-activated protein kinase (AMPK) by high density lipoprotein (HDL) and the role of AMPK in HDL-induced antiatherogenic actions were investigated. Experiments using genetic and pharmacological tools showed that HDL-induced activation of AMPKis dependent on both sphingosine 1-phosphate receptors andscavengerreceptorclassBtypeIthroughcalcium/calmodulindependent protein kinase kinase and, for scavenger receptor class B type I system, additionally serine-threonine kinase LKB1 in human umbilical vein endothelial cells. HDL-induced activation of Akt and endothelial NO synthase, stimulation of migration, and inhibition of monocyte adhesion and adhesion molecule expression were dependent on AMPK activation. The inhibitory role of AMPK in the adhesion molecule expression and monocyte adhesion on endothelium of mouse aorta was confirmed in vivo and ex vivo. On the other hand, stimulation of ERK and proliferation were hardly affected by AMPK knockdown but completely inhibited by an N17Ras, whereas the dominant-negative Ras was ineffective for AMPK activation. In conclusion, dual HDL receptor systems differentially regulate AMPKactivity through calcium/calmodulin-dependent protein kinase kinase and/or LKB1. Several HDL-induced antiatherogenic actions are regulated by AMPK, but proliferation-related actions are regulated by Ras rather than AMPK.

Original languageEnglish
Pages (from-to)4387-4397
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number7
DOIs
Publication statusPublished - 12 Feb 2010

Cite this

Kimura, T., Tomura, H., Sato, K., Ito, M., Matsuoka, I., Im, D. S., Kuwabara, A., Mogi, C., Itoh, H., Kurose, H., Murakami, M., & Okajima, F. (2010). Mechanism and role of high density lipoprotein-induced activation of AMP-activated protein kinase in endothelial cells. Journal of Biological Chemistry, 285(7), 4387-4397. https://doi.org/10.1074/jbc.M109.043869