Pro-Inflammatory Activation Promotes Atherogenic Endothelial Phenotype in Male and Female Human Umbilical Endothelial

Mario Lorenz1,2,3, Riwka Palant1,2,4, Edith Oscherowa1,5

  • 1Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.

Insights

Cellular sex drives early atherosclerosis differences. Male cells show increased focal adhesion proteins and inflammatory markers, while female cells uniquely upregulate IL-22, revealing hormone-independent vascular inflammation mechanisms.

Area of Science:

  • Cardiovascular Biology
  • Endothelial Cell Biology
  • Vascular Inflammation

Background:

  • Atherosclerosis is a leading cause of death, disproportionately affecting men.
  • Understanding sex-specific differences in early vascular inflammation is crucial for targeted therapies.

Purpose of the Study:

  • To investigate sex-specific, hormone-independent endothelial cell responses in early atherosclerosis.
  • To analyze differences in human umbilical vein endothelial cells (HUVECs) from opposite-sex twins.

Main Methods:

  • Pro-inflammatory stimulation of HUVECs with TNF-α and THP-1 cell supernatant.
  • Analysis of mRNA and protein expression of focal adhesion proteins, adhesion molecules, and cytokines.
  • Utilized opposite-sex twins to control for genetic background and minimize hormonal influence.

Main Results:

  • Male HUVECs showed increased mRNA for talin-I, vinculin, FAK, and α1-actinin; paxillin increased in both sexes.
  • Male HUVECs had higher VCAM-1, IL-1β, Flt-3L, G-CSF, and PDGF-AA induction.
  • Female HUVECs exclusively upregulated IL-22 secretion.

Conclusions:

  • Distinct cellular sex differences in endothelial phenotype contribute to early atherosclerosis.
  • These findings highlight cellular sex as a key factor in vascular inflammation, independent of systemic hormones.
  • Reveals mechanistic insights into sex disparities in atherosclerosis development.

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