Adiponectin limits monocytic microparticle-induced endothelial activation by modulation of the AMPK, Akt and NFκB

Mehroz Ehsan1, Krishna K Singh2, Fina Lovren3

  • 1Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Atherosclerosis
|December 22, 2015
PubMed
Abstract

Insights

Adiponectin limits the release and action of monocyte-derived microparticles (mono-MPs), which are linked to cardiovascular risk. This study reveals adiponectin

Area of Science:

  • Cardiovascular Biology
  • Inflammation Research
  • Adipokine Signaling

Background:

  • Monocyte-derived microparticles (mono-MPs) are implicated in linking cardiovascular risk factors to vascular injury.
  • Adiponectin is known for its anti-inflammatory and vasculoprotective properties.

Purpose of the Study:

  • To investigate the hypothesis that adiponectin limits the production and/or action of mono-MPs.
  • To elucidate the role of adiponectin in regulating inflammatory responses mediated by mono-MPs.

Main Methods:

  • Utilized flow cytometry and Western blot analyses on cell lines (THP-1), primary monocytes, and mouse models.
  • Evaluated the impact of adiponectin on lipopolysaccharide (LPS)-induced mono-MP release and associated inflammatory markers.
  • Assessed the effect of mono-MPs on endothelial cells (HUVECs) and the role of adiponectin in modulating these interactions.

Main Results:

  • Adiponectin significantly attenuated LPS-induced mono-MP release in vitro and in vivo.
  • Mice lacking adiponectin (Adipoq-/-) exhibited increased mono-MP generation compared to wild-type littermates.
  • Adiponectin reduced LPS-induced inflammasome activation (NLRP3, ASC, caspase-1, IL-1β) within MPs and abrogated MP-induced VCAM-1 expression and adhesion in HUVECs.
  • Mechanistically, adiponectin's effects involved the AMPK, Akt, and NFκB pathways.

Conclusions:

  • Adiponectin demonstrates a novel inhibitory effect on the production and action of mono-MPs.
  • These findings highlight another pleiotropic anti-inflammatory and vasculoprotective function of adiponectin.

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