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AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis

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A Correction to this article was published on 06 November 2021

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Abstract

Angiogenic factor with G patch and FHA domains 1 (AGGF1) is a newly identified proangiogenic protein, which plays an important role in vascular disease and angiogenesis. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. This study investigated whether AGGF1 is involved in the pathogenesis of mouse myocardial I/R injury and the underlying mechanisms. Wild-type (WT) C57BL/6 J mice were treated at 30 min prior to I/R injury with anti-AGGF1 neutralizing antibody (3 mg/kg) or recombinant human AGGF1 (rhAGGF1, 0.25 mg/kg). After I/R injury, the infarct size, the number of TUNEL-positive cardiomyocytes, Bax/Bcl2 ratio, inflammatory cytokine expression and angiogenesis were markedly increased as compared with sham control. Treatment of WT mice with anti-AGGF1 neutralizing antibody resulted in exaggeration of myocardial I/R injury but reducing angiogenesis. In contrast, administration of rhAGGF1 markedly reversed these effects. Furthermore, anti-AGGF1- or rhAGGF1-mediated effects on I/R-induced cardiac apoptosis, inflammation and angiogenesis were dose dependent. In addition, the protective effects of AGGF1 on cardiomyocyte apoptosis and inflammation were confirmed in cultured cardiomyocytes after I/R. Finally, these effects were associated with activation of ERK1/2, Stat3 and HIF-1α/VEGF pathways and inhibition of activation of NF-κB, p53 and JNK1/2 pathways. In conclusion, we report the first in vivo and in vitro evidence that AGGF1 reduces myocardial apoptosis and inflammation and enhances angiogenesis, leading to decreased infarct size after I/R injury. These results may provide a novel therapeutic approach for ischemic heart diseases.

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Acknowledgments

This work was supported by China National Natural Science Funds (No. 81025001, 81330003), Chang Jiang Scholar Program, and Beijing Higher Education Young Elite Teacher Project (YETP1668).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Physiology and Pathophysiology, Beijing AnZhen Hospital the Key Laboratory of Remodeling-Related Cardiovascular Diseases, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, China

    Yu Liu, Hui Yang, Lina Song, Nan Li, Qiu-Yue Han, Cui Tian, Jie Du & Hui-Hua Li

  2. Department of Cardiology, Chaoyang Hospital, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, China

    Cui Tian & Hui-Hua Li

  3. Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA, 19140, USA

    Erhe Gao

  4. Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China

    Yun-Long Xia

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  1. Yu Liu
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  2. Hui Yang
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  3. Lina Song
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  4. Nan Li
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  9. Yun-Long Xia
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Correspondence to Yun-Long Xia or Hui-Hua Li.

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Liu, Y., Yang, H., Song, L. et al. AGGF1 protects from myocardial ischemia/reperfusion injury by regulating myocardial apoptosis and angiogenesis. Apoptosis 19, 1254–1268 (2014). https://doi.org/10.1007/s10495-014-1001-4

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  • DOI: https://doi.org/10.1007/s10495-014-1001-4

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