Adiponectin limits monocytic microparticle-induced endothelial activation by modulation of the AMPK, Akt and NFκB signaling pathways. (February 2016)

• Record Type: Journal Article
• Authors: Ehsan, Mehroz; Singh, Krishna K.; Lovren, Fina; Pan, Yi; Quan, Adrian; Mantella, Laura-Eve; Sandhu, Paul; Teoh, Hwee; Al-Omran, Mohammed; Verma, Subodh
• Is Part Of: Atherosclerosis. Volume 245(2016)
• Page Start: 1
• Page End: 11
• Publication Date: 2016-02
• Subjects: Adiponectin -- AMPK -- Endothelial cell -- Monocyte -- Microparticles -- NFκB; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.11.024
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Objective: Monocyte-derived microparticles (mono-MPs) are emerging as critical transducers of inflammatory signals, and have been suggested to link cardiovascular risk factors to vascular injury. Since adiponectin has been proposed to exert multiple anti-inflammatory and vasculoprotective effects, we hypothesized that it might serve to limit the production and/or action of mono-MPs. Methods: Flow cytometry and western blot studies were conducted on THP-1 cells, THP-1-derived MPs, human umbilical vein endothelial cells (HUVECs), peripheral blood CD14+ monocytes and mice to evaluate the effects of adiponectin on mono-MPs. Results: Adiponectin attenuated lipopolysaccharide (LPS)-evoked MP release from THP-1 monocytes (30% difference) and peripheral blood monocytes (both P < 0.05) as well as dampened LPS-induced mono-MP generation in vivo . Furthermore, peritoneal monocytes from Adipoq −/− mice generated significantly greater MPs than those from Adipoq +/+ littermates in the absence (2.3 fold difference, P < 0.05) and presence (1.6 fold difference, P < 0.05) of LPS. LPS-induced MP expression of NLRP3 inflammasome and its key components, namely cleaved ASC, caspase-1 and IL-1β (pro- and cleaved), were markedly attenuated by adiponectin. HUVECs incubated with MPs from LPS-treated THP-1 cells exhibited increased VCAM-1 levels and adhesion to THP-1 cells. Adiponectin abrogated these effects. From a mechanistic standpoint, the effects of adiponectin on MP release and molecular signaling occurred at least in part through the AMPK, Akt and NFκB pathways. Conclusion: Adiponectin exerts novel effects to limit the production and action of mono-MPs, underscoring yet another pleiotropic effect of this adipokine. Highlights: Adiponectin limited the release of MPs from LPS-treated monocytes. Adiponectin attenuated LPS-induced MP expression of NLRP3 inflammasome. Adiponectin reduced mono-MP-evoked VCAM-1 expression and leukocyte-EC adhesion. Adiponectin regulates MP release in part via the AMPK, Akt and NFκB pathways.