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Human In Vitro Suppression as Screening Tool for the Recognition of an Early State of Immune Imbalance
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Immunosuppression Drugs Exhibit Differential Effects on Endothelial Cell Function.

Aly Elezaby1,2, Ryan Dexheimer1, David Wu1,3

  • 1Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA.

Journal of Vascular Research
|September 11, 2025
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Summary

Sirolimus and tacrolimus, common immunosuppression drugs, impact endothelial cell function differently. Sirolimus impairs cell migration and mitochondrial respiration, while tacrolimus affects nitric oxide release, revealing drug-specific vascular effects.

Keywords:
Endothelial cell functionImmunosuppressionTransplantVascular remodeling

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Area of Science:

  • Vascular Biology
  • Immunology
  • Stem Cell Biology

Background:

  • Immunosuppressive medications are crucial for managing neoplasms, autoimmune diseases, and organ transplants.
  • These drugs are known to induce adverse vascular remodeling.
  • Systemic drug effects complicate understanding cell-type-specific impacts on vasculature.

Purpose of the Study:

  • To investigate the effects of immunosuppression drugs on endothelial cell function.
  • To elucidate cell-type-specific drug impacts using a novel model.

Main Methods:

  • Utilized induced pluripotent stem cell-derived endothelial cells (iPSC-ECs).
  • Assessed endothelial cell functions including migration, proliferation, LDL uptake, mitochondrial respiration, and nitric oxide release.

Main Results:

  • Sirolimus significantly reduced endothelial cell migration, proliferation, acetylated LDL uptake, mitochondrial respiration, and angiogenic properties.
  • Tacrolimus was found to reduce nitric oxide release, with less impact on other functions compared to sirolimus.

Conclusions:

  • The iPSC-EC model effectively differentiates the effects of immunosuppression drugs on endothelial function.
  • Findings help elucidate mechanisms behind drug-induced adverse vascular profiles.
  • This research provides insights into managing vascular complications in patients on immunosuppressants.