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


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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Fig. 1
Fig. 2



ATP-binding cassette transporter


Adipocyte protein


CD163 antigen-like 1


Cholesterol efflux regulatory protein




Extracellular signal–regulated kinases


Fatty acid-binding proteins


c-Jun N-terminal kinase


Inducible nitric-oxide synthase


Mitogen-activated protein kinase


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


Selenoprotein P


Granulocyte-macrophage colony stimulating factor

IFN γ:

Interferon gamma




Low-density lipoprotein cholesterol




Liver X receptor alpha


Macrophage colony-stimulating factor


Nuclear factor (erythroid-derived 2)-like 2




Scavenger receptors


Tumor necrosis factor




Phosphoinositide 3-kinase


Peroxisome proliferator-activated receptor gamma


Reverse cholesterol transport


Reactive oxygen species




T helper 1


Toll-like receptors


Tumor necrosis factor alpha


Transforming growth factor β


Vascular smooth muscle cells


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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).

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