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

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.

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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

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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.

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Correspondence to Amir Abbas Momtazi-Borojeni or Banafsheh Nikfar.

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Momtazi-Borojeni, A.A., Abdollahi, E., Nikfar, B. et al. Curcumin as a potential modulator of M1 and M2 macrophages: new insights in atherosclerosis therapy. Heart Fail Rev 24, 399–409 (2019). https://doi.org/10.1007/s10741-018-09764-z

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Keywords

  • Atherosclerosis
  • Atherosclerotic plaque
  • Curcumin
  • Inflammation
  • M1 and M2 macrophages