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Curcumin as a potential modulator of M1 and M2 macrophages: new insights in atherosclerosis therapy

  • Amir Abbas Momtazi-BorojeniEmail author
  • Elham Abdollahi
  • Banafsheh NikfarEmail author
  • Shahla Chaichian
  • Mahnaz Ekhlasi-Hundrieser
Article
  • 146 Downloads

Abstract

Accumulation of macrophages within the artery wall is an eminent feature of atherosclerotic plaques. Macrophages are influenced by various plaque microenvironmental stimuli, such as oxidized lipids, cytokines, and senescent erythrocytes, and thereby polarize into two main phenotypes called proinflammatory M1 and anti-inflammatory M2 macrophages. In the hemorrhagic zones of atheroma, upon exposure to iron, sequestration of iron by M1 macrophages results in an uncontrolled proinflammatory phenotype impairing wound healing, while M2 macrophages phagocytose both apoptotic cells and senescent erythrocytes. M1 macrophages are prominent phenotype in the unstable plaques, in which plaque shoulder contains macrophages mainly present markers of M1 phenotype, whereas the fibrous cap encompassing the necrotic lipid core content macrophages expressed markers of both M1 and M2 subtypes. The abovementioned findings suggest macrophage modulation as a potent approach for atherosclerosis therapy. Curcumin is a polyphenol dietary derived from turmeric with numerous pharmacological activities. Recent in vitro and in vivo studies have indicated that curcumin exerted lipid-lowering effects, and also can modulate function of different macrophage subsets in various macrophage-involved diseases. The current review aimed to present role of macrophage subtypes in atherosclerosis development and progression, and to understand effect of curcumin on macrophage polarization and foam cell formation in the atherosclerosis lesions. Overall, we would address important targets for macrophage modulation in atherosclerotic plaques.

Keywords

Atherosclerosis Atherosclerotic plaque Curcumin Inflammation M1 and M2 macrophages 

Abbreviations

ABCA1

ATP-binding cassette transporter

aP2

Adipocyte protein

CD163L1

CD163 antigen-like 1

CERP

Cholesterol efflux regulatory protein

COX-2

Cyclooxygenase-2

ERK

Extracellular signal–regulated kinases

FABPs

Fatty acid-binding proteins

JNK

c-Jun N-terminal kinase

iNOS

Inducible nitric-oxide synthase

MAPK

Mitogen-activated protein kinase

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

SEPP

Selenoprotein P

GM-CSF

Granulocyte-macrophage colony stimulating factor

IFN γ

Interferon gamma

IL

Interleukin

LDL-C

Low-density lipoprotein cholesterol

LPS

Lipopolysaccharide

LXR-α

Liver X receptor alpha

M-CSF

Macrophage colony-stimulating factor

NFE2L2

Nuclear factor (erythroid-derived 2)-like 2

Ox-LDL

Oxidized-LDL

SR

Scavenger receptors

TNF

Tumor necrosis factor

LPS

Llipopolysaccharide

PI3K

Phosphoinositide 3-kinase

PPAR-γ

Peroxisome proliferator-activated receptor gamma

RCT

Reverse cholesterol transport

ROS

Reactive oxygen species

S1P

Sphingosine-1-phosphate

Th1

T helper 1

TLRs

Toll-like receptors

TNF-α

Tumor necrosis factor alpha

TGF-β

Transforming growth factor β

VSMCs

Vascular smooth muscle cells

Notes

Acknowledgments

The authors would like to say special thanks to the cooperation of Pars Advanced and Minimally Invasive Medical Manners Research Center - Pars Hospital, Nanotechnology Research Center, and Department of Medical Biotechnology of Mashhad University of Medical Sciences for their kindness.

Compliance with ethical standards

Conflict of interest

The authors have no direct conflict of interests related to the content of this review.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Halal research center of IRIFDATehranIran
  2. 2.Nanotechnology Research Center, Bu-Ali Research Institute, Student Research CommitteeMashhad University of Medical SciencesMashhadIran
  3. 3.Department of Medical Immunology, Student Research Committee, School of MedicineMashhad University of Medical SciencesMashhadIran
  4. 4.Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars HospitalIran University of Medical SciencesTehranIran
  5. 5.Minimally Invasive Techniques Research Center in Women, Tehran Medical Sciences BranchIslamic Azad UniversityTehranIran
  6. 6.Endometriosis Research Center, Iran University of Medical SciencesTehranIran
  7. 7.Werlhof-InstitutHannoverGermany

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