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How many cadherins do human endothelial cells express?

  • Natalia Colás-Algora
  • Jaime MillánEmail author
Review

Abstract

The vasculature is the paradigm of a compartment generated by parallel cellular barriers that aims to transport oxygen, nutrients and immune cells in complex organisms. Vascular barrier dysfunction leads to fatal acute and chronic inflammatory diseases. The endothelial barrier lines the inner side of vessels and is the main regulator of vascular permeability. Cadherins comprise a superfamily of 114 calcium-dependent adhesion proteins that contain conserved cadherin motifs and form cell–cell junctions in metazoans. In mature human endothelial cells, only VE (vascular endothelial)-cadherin and N (neural)-cadherin have been investigated in detail. Although both cadherins are essential for regulating endothelial permeability, no comprehensive expression studies to identify which other family members could play a relevant role in endothelial cells has so far been performed. Here, we have reviewed gene and protein expression databases to analyze cadherin expression in mature human endothelium and found that at least 24 cadherin superfamily members are significantly expressed. Based on data obtained from other cell types, organisms and experimental models, we discuss their potential functions, many of them unrelated to the formation of endothelial cell–cell junctions. The expression of this new set of endothelial cadherins highlights the important but still poorly defined roles of planar cell polarity, the Hippo pathway and mitochondria metabolism in human vascular homeostasis.

Keywords

Cadherin Gene expression Endothelium Vascular permeability Barrier function Cell adhesion molecule 

Abbreviations

APP

Amyloid precursor protein

CCM

Cerebral cavernous malformation

CDHR

Cadherin-related proteins

CLSTN

Calsyntenin

DCHS1

Dachsous cadherin related 1

E-cadherin

Epithelial cadherin

EMT

Epithelial–mesenchymal transition

EndMT

Endothelial–mesenchymal transition

GDNF

Glial cell line-derived neurotrophic factor

GPI

Glycosylphosphatidylinositol

HCV

Hepatitis C virus

HUVEC

Human umbilical vein endothelial cells

KSHV

Kaposi ́s sarcoma-associated herpesvirus

MUCDHL

Mucin and cadherin-like

N-cadherin

Neural cadherin

OB-cadherin

Osteoblast-cadherin

PCDH

Protocadherin

PCDHG

Protocadherin gamma (cluster)

PCP

Planar cell polarity

phEndEC

Primary human endoneurial endothelial cells

RET

Rearranged during transfection

SMAD3

Small and mothers against decapentaplegic 3

TGF- β

Transforming growth factor-β

VE-cadherin

Vascular endothelial cadherin

WNT

Wingless-related integration site

YAP

Yes-associated protein

TAZ

Transcriptional coactivator with PDZ-binding motif

7D cadherin

7-Domain cadherin

Notes

Acknowledgments

We thank Cristina Cacho Navas and Dr. Nahuel Ramella for the critical reading of the manuscript and the Genomics Facility at the CBMSO for its helpful advice. We also thank Dr. Phil Mason, who provided English language support.

Funding

The work was supported by Grants SAF2017-88187-R from MINECO, B2017/BMD-3817 from Comunidad de Madrid and Endocornea 2, collaborative agreement with CSIC, funded by Instituto de Investigación Fundación Jiménez Díaz. N.C.A. is a recipient of an FPU fellowship from MECD.

Compliance with ethical standards

Conflict of interest

The authors declare that no conflict of interest exists.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones CientíficasUniversidad Autónoma de MadridMadridSpain

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