Cholesterol crystals promote endothelial cell and monocyte interactions via H 2 O 2 -mediated PP2A inhibition, NFκB activation and ICAM1 and VCAM1 expression

Prahalathan Pichavaram, Arul M. Mani, Nikhlesh Singh, Rao Gadiparthi

Research output: Contribution to journalArticle

Abstract

In the present study, we show that cholesterol crystals induce NFκB activation, and ICAM1 and VCAM1 expression via xanthine oxidase-mediated H 2 O 2 production and PP2A inhibition in influencing endothelial cell and monocyte interactions and all these adverse effects of cholesterol crystals could be attenuated by proresolving lipid mediator RvD1. In addition, feeding mice with cholesterol rich diet (CRD) increased xanthine oxidase expression, its activity and H 2 O 2 production leading to PP2A inhibition, NFκB activation, and ICAM1 and VCAM1 expression and RvD1 attenuated all these effects of CRD substantially. Furthermore, peripheral blood mononuclear cells (PBMCs) from wild type mice when injected into mice that were fed with CRD or RvD1 + CRD showed increased leukocyte trafficking to arteries of CRD-fed mice as compared to RvD1 + CRD mice. These findings suggest that cholesterol crystals via promoting oxidant stress and inhibiting Ser/Thr phosphatases such as PP2A stimulate NFκB activation and ICAM1 and VCAM1 expression, and thereby enhance EC-monocyte interactions. In addition, proresolving lipid mediators such as RvD1 appear to exert their anti-inflammatory effects via countering the adverse effects of cholesterol crystals or CRD.

Original languageEnglish (US)
Article number101180
JournalRedox Biology
Volume24
DOIs
StatePublished - Jun 1 2019

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Endothelial cells
Cell Communication
Monocytes
Endothelial Cells
Chemical activation
Cholesterol
Nutrition
Crystals
Diet
Xanthine Oxidase
Lipids
Phosphoric Monoester Hydrolases
Oxidants
Blood Cells
Leukocytes
Blood
Anti-Inflammatory Agents
Arteries

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Organic Chemistry

Cite this

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title = "Cholesterol crystals promote endothelial cell and monocyte interactions via H 2 O 2 -mediated PP2A inhibition, NFκB activation and ICAM1 and VCAM1 expression",
abstract = "In the present study, we show that cholesterol crystals induce NFκB activation, and ICAM1 and VCAM1 expression via xanthine oxidase-mediated H 2 O 2 production and PP2A inhibition in influencing endothelial cell and monocyte interactions and all these adverse effects of cholesterol crystals could be attenuated by proresolving lipid mediator RvD1. In addition, feeding mice with cholesterol rich diet (CRD) increased xanthine oxidase expression, its activity and H 2 O 2 production leading to PP2A inhibition, NFκB activation, and ICAM1 and VCAM1 expression and RvD1 attenuated all these effects of CRD substantially. Furthermore, peripheral blood mononuclear cells (PBMCs) from wild type mice when injected into mice that were fed with CRD or RvD1 + CRD showed increased leukocyte trafficking to arteries of CRD-fed mice as compared to RvD1 + CRD mice. These findings suggest that cholesterol crystals via promoting oxidant stress and inhibiting Ser/Thr phosphatases such as PP2A stimulate NFκB activation and ICAM1 and VCAM1 expression, and thereby enhance EC-monocyte interactions. In addition, proresolving lipid mediators such as RvD1 appear to exert their anti-inflammatory effects via countering the adverse effects of cholesterol crystals or CRD.",
author = "Prahalathan Pichavaram and Mani, {Arul M.} and Nikhlesh Singh and Rao Gadiparthi",
year = "2019",
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T1 - Cholesterol crystals promote endothelial cell and monocyte interactions via H 2 O 2 -mediated PP2A inhibition, NFκB activation and ICAM1 and VCAM1 expression

AU - Pichavaram, Prahalathan

AU - Mani, Arul M.

AU - Singh, Nikhlesh

AU - Gadiparthi, Rao

PY - 2019/6/1

Y1 - 2019/6/1

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AB - In the present study, we show that cholesterol crystals induce NFκB activation, and ICAM1 and VCAM1 expression via xanthine oxidase-mediated H 2 O 2 production and PP2A inhibition in influencing endothelial cell and monocyte interactions and all these adverse effects of cholesterol crystals could be attenuated by proresolving lipid mediator RvD1. In addition, feeding mice with cholesterol rich diet (CRD) increased xanthine oxidase expression, its activity and H 2 O 2 production leading to PP2A inhibition, NFκB activation, and ICAM1 and VCAM1 expression and RvD1 attenuated all these effects of CRD substantially. Furthermore, peripheral blood mononuclear cells (PBMCs) from wild type mice when injected into mice that were fed with CRD or RvD1 + CRD showed increased leukocyte trafficking to arteries of CRD-fed mice as compared to RvD1 + CRD mice. These findings suggest that cholesterol crystals via promoting oxidant stress and inhibiting Ser/Thr phosphatases such as PP2A stimulate NFκB activation and ICAM1 and VCAM1 expression, and thereby enhance EC-monocyte interactions. In addition, proresolving lipid mediators such as RvD1 appear to exert their anti-inflammatory effects via countering the adverse effects of cholesterol crystals or CRD.

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