Endothelial cell responses in sepsis are attenuated by targeting truncated procalcitonin

Sepsis is associated with hypotension, vascular leakage, vasoplegia and microvascular dysfunction. Therefore, the endothelium is a target for sepsis therapies. Since truncated procalcitonin exerts vascular activity, we here evaluated the efficacy of targeting procalcitonin for vascular integrity and sepsis outcomes. Sepsis up-regulated >2000 genes involved in pro-inflammatory responses while similar numbers of genes involving cell growth and maintenance were down-regulated. Transcriptomic changes in endothelial cells diminished by >50% by anti-procalcitonin antibodies and this was functionally associated with preserved vascular barrier integrity in lungs and intestines, reduced sepsis-induced vasoplegia, preserved endothelial nitric oxide bioavailability, improved organ integrity and reduced sepsis severity in mice. Mechanistically, procalcitonin neutralization was associated with reduced signaling of the interleukin-17 pathway. We here show sepsis induces substantial changes to the endothelial transcriptome and vascular integrity and neutralizing procalcitonin is a suitable means to preserve endothelial homeostasis at a transcriptomic and functional level that could translate into organ protection during sepsis.

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Publication Details

Journal
Nature Communications
Published
2026-01-21
DOI
https://doi.org/10.1038/s41467-025-68199-x
Primary Topic
Sepsis Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Endothelial cell responses in sepsis are attenuated by targeting truncated procalcitonin

Vera Rauschenberger, Dietmar Vestweber, Astrid F. Nottebaum, Laura Brabenec et al.
Nature Communications
Sepsis Diagnosis and Treatment
article

Endothelial cell responses in sepsis are attenuated by targeting truncated procalcitonin

Vera Rauschenberger, Dietmar Vestweber, Astrid F. Nottebaum, Laura Brabenec, Nicolas Schlegel, Laura Cyran, Sebastian Kintrup, Philipp Burkard, Klaus Schughart, Katharina E. M. Hellenthal, Stefanie Kampmeier, Nana-Maria Wagner, Patrick Meybohm, Stefan Wagner
article en

Abstract

Sepsis is associated with hypotension, vascular leakage, vasoplegia and microvascular dysfunction. Therefore, the endothelium is a target for sepsis therapies. Since truncated procalcitonin exerts vascular activity, we here evaluated the efficacy of targeting procalcitonin for vascular integrity and sepsis outcomes. Sepsis up-regulated >2000 genes involved in pro-inflammatory responses while similar numbers of genes involving cell growth and maintenance were down-regulated. Transcriptomic changes in endothelial cells diminished by >50% by anti-procalcitonin antibodies and this was functionally associated with preserved vascular barrier integrity in lungs and intestines, reduced sepsis-induced vasoplegia, preserved endothelial nitric oxide bioavailability, improved organ integrity and reduced sepsis severity in mice. Mechanistically, procalcitonin neutralization was associated with reduced signaling of the interleukin-17 pathway. We here show sepsis induces substantial changes to the endothelial transcriptome and vascular integrity and neutralizing procalcitonin is a suitable means to preserve endothelial homeostasis at a transcriptomic and functional level that could translate into organ protection during sepsis.

Nature CommunicationsVol. 17(1)
Harvard University (US), University of Tennessee Health Science Center (US), Johannes Gutenberg University Mainz (DE), University of Münster (DE), Karolinska Institutet (SE), Massachusetts General Hospital (US), University Medical Center of the Johannes Gutenberg University Mainz (DE), University Hospital Münster (DE), Universitätsklinikum Würzburg (DE), Max Planck Institute for Molecular Biomedicine (DE), FH Münster University of Applied Sciences (DE), University of Birmingham (GB)
Deutsche Forschungsgemeinschaft
Good health and well-being
Openalex Percentile: Top 82%
Sepsis Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
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