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Copper Preserves Vasculature Structure and Function by Protecting Endothelial Cells from Apoptosis in Ischemic Myocardium

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Abstract

The present study was undertaken to investigate whether Cu protects vasculatures from ischemic injury in the heart. C57/B6 mice were introduced to myocardial ischemia (MI) by permanent ligation of the left anterior descending (LAD) coronary artery. Two hours post-LAD ligation, mice were intravenously injected with a Cu-albumin (Cu-alb) solution, or saline as control. At 1, 4, or 7 days post-MI, hearts were collected for further analysis. A dramatic decrease in CD31-positive endothelial cells concomitantly with abundant apoptosis, along with obstruction of blood flow, was observed in ischemic myocardium 1 day post-MI. The early Cu-alb treatment protected CD31-positive cells from apoptosis, along with a preservation of micro-vessels and a decrease in infarct size. This early vasculature preservation ensured myocardial blood perfusion and protected cardiac contractile function until 28 days post-MI. This strategy of Cu-alb treatment immediately following MI would help develop a therapeutic approach for acute heart attack patients in a clinical setting.

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Abbreviations

AAS:

Atomic absorption spectrometry

BSA:

Bovine serum albumin

CCS-1:

Cu chaperone for superoxide dismutase-1

Cu:

Copper

Cu-alb:

Cu-albumin

ECs:

Endothelial cells

EF:

Ejection fraction

FS:

Fractional shortening

HIF-1:

Hypoxia-inducible factor-1

HSA:

Human serum albumin

IA:

Ischemic area

LAD:

Left anterior descending of coronary artery

LVEDV:

Left ventricular end-diastolic volume

LVESV:

Left ventricular end-systolic volume

LVIDd:

Left ventricular internal diameter at diastolic phase

LVIDs:

Left ventricular internal diameter at systolic phase

MI:

Myocardial ischemia

OCT:

Optimal cutting temperature gel

ROS:

Reactive oxygen species

RM:

Remote myocardium from ischemia

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay

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Acknowledgements

The authors thank Dr. Jiaming Liu, Mr. Yi Ren, Ms. Qin Sheng, and Ms. Yuan Ma for assistance in animal care and surgery and thank Ms. Fang Nan for technique support in histological analysis.

Funding

This work was supported by China Postdoctoral Science Foundation (No. 2020M673261).

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Author notes

  1. Ying Xiao and Xin Song contributed equally to this work.

Authors and Affiliations

  1. Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, 610041, People’s Republic of China

    Ying Xiao, Xin Song, Tao Wang, Xia Meng, Qipu Feng, Kui Li & Y. James Kang

  2. Memphis Institute of Regenerative Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA

    Y. James Kang

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Contributions

Y.X., X.S., T.W., and Y.J.K. designed the experiments; Y.X., X.S., T.W., X.M., Q.F., X.S., and K.L. carried out the experiments, data analysis, and result interpretation; Y.J.K. and Y.X. drafted the manuscript; Y.J.K. revised the draft and approved the final version of the manuscript.

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Correspondence to Y. James Kang.

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No human studies were carried out by the authors for this article. All institutional and national guidelines for the care and use of laboratory animals were followed and approved by Institutional Animal Care and Use Committee (IACUC) of Sichuan University West China Hospital (Approval No. 2020238A).

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Xiao, Y., Song, X., Wang, T. et al. Copper Preserves Vasculature Structure and Function by Protecting Endothelial Cells from Apoptosis in Ischemic Myocardium. J. of Cardiovasc. Trans. Res. 14, 1146–1155 (2021). https://doi.org/10.1007/s12265-021-10128-6

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