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Activating transcription factor 3 in cardiovascular diseases: a potential therapeutic target

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Abstract

Cardiovascular diseases (CVDs) are the primary causes of death worldwide. Among the numerous signaling molecules involved in CVDs, transcriptional factors directly influence gene expression and play a critical role in regulating cell function and the development of diseases. Activating transcription factor (ATF) 3 is an adaptive-response gene in the ATF/cAMP responsive element-binding (CREB) protein family of transcription factors that acts as either a repressor or an activator of transcription via the formation of homodimers or heterodimers with other ATF/CREB members. A appropriate ATF3 expression is important for the normal physiology of cells, and dysfunction of ATF3 is associated with various pathophysiological responses such as inflammation, apoptosis, oxidative stress and endoplasmic reticulum stress, and diseases, including CVDs. This review focuses on the role of ATF3 in cardiac hypertrophy, heart failure, atherosclerosis, ischemic heart diseases, hypertension and diabetes mellitus to provide a novel therapeutic target for CVDs.

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Abbreviations

ALK:

Activin receptor-like kinase

Ang II:

Angiotensin II

ATF:

Activating transcription factor

bZIP:

Basic-region leucine zipper

CRE:

cAMP responsive element

CREB:

cAMP responsive element binding

CVDs:

Cardiovascular diseases

CXCL:

C-X-C motif chemokine ligand

CXCR:

C-X-C motif chemokine receptor

DM:

Diabetes mellitus

DOX:

Doxorubicin

ECs:

Endothelial cells

EGFR:

Epidermal growth factor receptor

Egr1:

Early growth response protein 1

ERK:

Extracellular signal-regulated kinase

ET-1:

Endothelin-1

HDL:

High-density lipoprotein

HF:

Heart failure

HFD:

High-fat diet

HUVECs:

Human umbilical vein endothelial cells

ICAM:

Intercellular cell adhesion molecule

IFNγ:

Interferon γ

IHD:

Ischemic heart diseases

IL:

Interleukin

IP:

Ischemic preconditioning

I/R:

Ischemia/reperfusion

IRF7:

Interferon regulatory factor 7

JNK:

c-Jun N-terminal kinase

KLF:

Krueppel-like factor

KO:

Knockout

LPC:

Lysophosphatidylcholine

LPS:

Lipopolysaccharide

Map2K3:

Mitogen-activated protein kinase kinase 3

MED:

Methionine-enriched diet

MEK:

MAPK/ERK kinase

MI:

Myocardial infarction

MKK7:

MAPK kinase 7

MMPs:

Matrix metalloproteinases

NAFLD:

Non-alcoholic fatty liver disease

NF-κB:

Nuclear factor-κB

NO:

Nitric oxide

oxLDL:

Oxidized low-density lipoprotein

PCNA:

Proliferating cell nuclear antigen

PE:

Phenylephrine

PI3K:

Phosphatidylinositol 3-kinase

PKA:

Protein kinase A

SAPK:

Stress-activated protein kinase

SMCs:

Smooth muscle cells

tBHQ:

tert-Butylhydroquinone

TGF-β:

Transforming growth factor-β

TGRL:

Triglyceride-rich lipoproteins

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

T2DM:

Type 2 DM

VSMCs:

Vascular smooth muscle cells

ZDF:

Zucker Diabetic Fatty

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81300070, 81770399, 81470516 and 81530012), the Fundamental Research Funds for the Central Universities of China (2042018kf0121), the Development Center for Medical Science and Technology National Health and Family Planning Commission of China (2016ZX-008-01), and the National Major Scientific Instrument and Equipment Development Projects of China (2013YQ03092306).

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  1. Department of Cardiology, Renmin Hospital of Wuhan University, JieFang Road 238, Wuhan, 430060, People’s Republic of China

    Heng Zhou, Ning Li, Yuan Yuan, Ya-Ge Jin, Wei Deng & Qi-Zhu Tang

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

    Heng Zhou, Ning Li, Yuan Yuan, Ya-Ge Jin, Wei Deng & Qi-Zhu Tang

  3. Hubei Key Laboratory of Cardiology, Wuhan, 430060, People’s Republic of China

    Heng Zhou, Ning Li, Yuan Yuan, Ya-Ge Jin, Wei Deng & Qi-Zhu Tang

  4. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China

    Haipeng Guo

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  1. Heng Zhou
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  2. Ning Li
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Zhou, H., Li, N., Yuan, Y. et al. Activating transcription factor 3 in cardiovascular diseases: a potential therapeutic target. Basic Res Cardiol 113, 37 (2018). https://doi.org/10.1007/s00395-018-0698-6

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