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Zinc Homeostasis Alters Zinc Transporter Protein Expression in Vascular Endothelial and Smooth Muscle Cells

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Abstract

Introduction

Zinc is an important essential micronutrient with anti-oxidative and anti-inflammatory properties in humans. The role of zinc in signalling has been characterized in the nervous, endocrine, gastrointestinal, renal and reproductive systems. Relatively little is known regarding its role in the vascular system, but the role of zinc homeostasis in augmenting vascular health and vasorelaxation is emerging. Zinc transport proteins are integral to the protective function of zinc, but knowledge of their expression in vascular endothelial and smooth muscle cells is lacking.

Methodology

Human coronary artery endothelial cells and pulmonary artery smooth muscle cells were assessed for gene expression (RT-PCR) of SLC39A (ZIP), SLC30A (ZnT) and metallothionein (MT) families of Zn transporters and storage proteins. Protein expression (fluorescence confocal microscopy) was then analysed for the proteins of interest that changed mRNA expression: ZIP2, ZIP12, ZnT1, ZnT2 and MT1/2.

Results

Endothelial and smooth muscle cell mRNA expression of ZnT1, ZnT2 and MT1 was significantly downregulated by low and high Zn conditions, while ZIP2 and ZIP12 expression was induced by Zn depletion with the Zn chelator, TPEN. Changes in gene expression were consistent with protein expression levels for ZIP2, ZIP12 and MT1, where ZIP2 was localized to intracellular bodies and ZIP12 to lamellipodia.

Conclusion

Vascular endothelial and smooth muscle cells actively regulate specific Zn transport and metallothionein gene and protein expressions to achieve Zn homeostasis.

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Abbreviations

ZnT:

Zinc transporter

ZIP:

Zrt- and Irt-like protein

MT:

Metallothionein

XIAP:

X-linked inhibitor of apoptosis protein

RAC1:

Ras-related C3 botulinum toxin substrate 1

HCAEC:

Human coronary artery endothelial cells

HPASMC:

Human pulmonary artery endothelial cells

CVD:

Cardiovascular disease

TPEN:

N,N,N′,N′-Tetrakis(2-pyridinylmethyl)-1,2-ethanediamine

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Funding

This study was supported by the National Health and Medical Research Council (Project number APP1138917). The funders had no role in the study design, data collection, analysis or interpretation, manuscript preparation or decision to publish.

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  1. Adrian I. Abdo and Hai Bac Tran contributed equally to this work.

Authors and Affiliations

  1. Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, 28 Woodville Rd, Woodville South, SA, 5011, Australia

    Adrian I. Abdo, John F. Beltrame & Peter D. Zalewski

  2. Faculty of Health and Medical Sciences, University of Adelaide, 4 North Terrace, Adelaide, SA, 5000, Australia

    Adrian I. Abdo, Hai Bac Tran, Sandra Hodge, John F. Beltrame & Peter D. Zalewski

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  1. Adrian I. Abdo
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Abdo, A.I., Tran, H.B., Hodge, S. et al. Zinc Homeostasis Alters Zinc Transporter Protein Expression in Vascular Endothelial and Smooth Muscle Cells. Biol Trace Elem Res 199, 2158–2171 (2021). https://doi.org/10.1007/s12011-020-02328-z

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