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.
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This work was supported by China Postdoctoral Science Foundation (No. 2020M673261).
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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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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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DOI: https://doi.org/10.1007/s12265-021-10128-6