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Endothelial barrier function is differentially regulated by CEACAM1-mediated signaling.

Sharang Ghavampour1, Florian Kleefeldt1, Heike Bömmel1

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FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 11, 2018
PubMed
Summary

Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) deficiency disrupts endothelial homeostasis, increasing leukocyte adhesion and altering the endothelial barrier function. This CEACAM1 role in adult vessels impacts plaque formation and vascular health.

Keywords:
adherenceatherosclerosiseNOSendothelial dysfunctionvascular permeability

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Area of Science:

  • Vascular Biology
  • Cellular Biology
  • Immunology

Background:

  • Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is vital for blood vessel formation.
  • CEACAM1 deficiency leads to aortic plaque-like lesions, suggesting a role in adult vasculature.
  • Mechanisms underlying CEACAM1's function in adult vessels are not fully understood.

Purpose of the Study:

  • To investigate the role of CEACAM1 in maintaining endothelial homeostasis in adult blood vessels.
  • To elucidate how CEACAM1 influences endothelial barrier function and leukocyte-endothelial interactions.

Main Methods:

  • Analysis of CEACAM1-deficient mouse models.
  • Assessment of endothelial cell eNOS redistribution and endothelial glycocalyx alterations.
  • Evaluation of leukocyte-endothelial interactions and endothelial barrier permeability.
  • Investigation of CEACAM1's impact on β-catenin and caveolin-1 phosphorylation.

Main Results:

  • CEACAM1 deficiency caused eNOS redistribution and altered the endothelial glycocalyx, increasing leukocyte adhesion.
  • CEACAM1's effect on endothelial barrier leakiness was age-dependent, being protective in young mice but detrimental in aged mice.
  • CEACAM1 modulated phosphorylation of β-catenin and caveolin-1, key regulators of endothelial barrier function.

Conclusions:

  • CEACAM1 plays a critical role in maintaining endothelial homeostasis in adult blood vessels.
  • Dysregulation of CEACAM1 contributes to increased inflammation and potential plaque formation by affecting endothelial barrier integrity and leukocyte interactions.
  • CEACAM1 signaling differentially regulates endothelial barrier function based on age.