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Critical roles of macrophages in pressure overload-induced cardiac remodeling

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Abstract

Macrophages are integral components of the mammalian heart that show extensive expansion in response to various internal or external stimuli. After the onset of sustained pressure overload (PO), the accumulation of cardiac macrophages through local macrophage proliferation and monocyte migration has profound effects on the transition to cardiac hypertrophy and remodeling. In this review, we describe the heterogeneity and diversity of cardiac macrophages and summarize the current understanding of the important roles of macrophages in PO-induced cardiac remodeling. In addition, the possible mechanisms involved in macrophage modulation are also described. Finally, considering the significant effects of cardiac macrophages, we highlight their emerging role as therapeutic targets for alleviating pathological cardiac remodeling after PO.

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Abbreviations

AAC:

Abdominal aortic constriction

Ang II:

Angiotensin II

CCL:

C-C motif chemokine ligand

CCR:

C-C motif chemokine receptor

CD:

Cluster of differentiation

CM:

Cardiomyocyte

CSF2:

Colony-stimulating factor 2

CX3C:

C-X3-C motif chemokine

CXCL:

Chemokine (C-X-C motif) ligand

CXCR:

C-X-C motif chemokine receptor

DNMT3A:

DNA methyltransferase 3 alpha

GATA3:

GATA binding protein 3

HF:

Heart failure

HIF:

Hypoxia inducible factor

HLA:

Human leukocyte antigen

ICAM1:

Intercellular cell adhesion molecule 1

IFN–γ:

Interferon gamma

IM:

Interstitial macrophage

KO:

Knockout

LFA-1:

Lymphocyte function-associated antigen-1

M-CSF:

Macrophage-colony stimulating factor

MI:

Myocardial infarction

MIF:

Macrophage migration inhibitory factor

NLRP3:

NLR family pyrin domain containing 3

PHD:

Prolyl hydroxylase domain

PI3K:

Phosphatidylinositol 3-kinase

PO:

Pressure overload

RAS:

Renin-angiotensin system

RHOA:

Ras homolog family member A

SNP:

Single nucleotide polymorphism

TAC:

Transverse aortic constriction

TET2:

Tet methylcytosine dioxygenase 2

TNFα:

Tumor necrosis factor α

TRAF6:

TNF receptor-associated factor 6

XCL:

Chemokine (X-C motif) ligand

WT:

Wild type

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81900219, 81530012, 81800216), the Fundamental Research Funds for the Central Universities (2042019kf0062, 2042018kf1032), Development Center for Medical Science and Technology National Health and Family Planning Commission of the People’s Republic of China (2016ZX-008-01), and National Key R&D Program of China (2018YFC1311300).

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  1. Dan Yang and Han-Qing Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China

    Dan Yang, Fang-Yuan Liu, Nan Tang, Zhen Guo, Shu-Qing Ma, Peng An, Ming-Yu Wang, Hai-Ming Wu, Zheng Yang, Di Fan & Qi-Zhu Tang

  2. Cardiovascular Research Institute, Wuhan University, Jiefang Road 238, Wuhan, 430060, People’s Republic of China

    Dan Yang, Fang-Yuan Liu, Nan Tang, Zhen Guo, Shu-Qing Ma, Peng An, Ming-Yu Wang, Hai-Ming Wu, Zheng Yang, Di Fan & Qi-Zhu Tang

  3. Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, 430060, People’s Republic of China

    Dan Yang, Fang-Yuan Liu, Nan Tang, Zhen Guo, Shu-Qing Ma, Peng An, Ming-Yu Wang, Hai-Ming Wu, Zheng Yang, Di Fan & Qi-Zhu Tang

  4. Department of Thyroid and Breast, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China

    Han-Qing Liu

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  1. Dan Yang
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Contributions

Dan Yang, Han-Qing Liu, Di Fan, and Qi-Zhu Tang contributed to the conception and design of the review; Fang-Yuan Liu, Nan Tang, Zhen Guo, Shu-Qing Ma, Peng An, and Ming-Yu Wang performed the literature search and data analysis; the first draft of the manuscript was written by Dan Yan and Han-Qing Liu; Hai-Ming Wu, Zheng Yang, Di Fan, and Qi-Zhu Tang critically revised the manuscript. All authors contributed to the article and approved the submitted version.

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Correspondence to Di Fan or Qi-Zhu Tang.

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Yang, D., Liu, HQ., Liu, FY. et al. Critical roles of macrophages in pressure overload-induced cardiac remodeling. J Mol Med 99, 33–46 (2021). https://doi.org/10.1007/s00109-020-02002-w

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