Sex-based differences in fibrosis markers in human abdominal aortic aneurysms
8 affiliations
- 1Division of Vascular Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
- 2Cardiovascular Research Innovation in Surgery and Engineering Center, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
- 3Division of Gastroenterology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
- 4Veterans Affairs St. Louis Health Care System, St. Louis, MO, USA.
- 5Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
- 6Division of Molecular Cell Biology, Washington University School of Medicine, St. Louis, MO, USA.
- 7Division of Surgical Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
- 8Department of Biomedical Engineering, McKelvey School of Engineering, Washington University School of Medicine, St. Louis, MO, USA.
Abstract
Background: Abdominal aortic aneurysms (AAA) are a complex degenerative vascular disease. The role of fibrosis in AAA progression is unclear. Our study evaluated the impact of fibroblast activation protein (FAP), collagen, and vimentin on AAA fibrosis and progression. We hypothesized that FAP may influence fibrosis and disease severity in AAA, with potential sex-specific differences. Study Design: Multi-centered transcriptomic analysis of aortic samples from 15 human AAA and 5 non-AAA was performed to evaluate cell-specific fibrosis gene expression profiles. Histopathological and molecular analysis of 26 male and female AAA samples (mAAA and fAAA) and 29 male and female normal abdominal aortas (mNAA and fNAA) was performed to assess whole-tissue fibrosis markers and signaling. Results: Single-cell RNA sequencing (scRNA-seq) analysis identified eight major cell clusters with distinct sex-based distributions. Although vascular smooth muscle cells (VSMCs) and fibroblast clusters had reduced counts in both male and female AAAs, they more highly expressed FAP and COL1A1 genes, particularly in females. Whole-tissue analysis demonstrated elevated extracellular matrix deposits with markedly increased collagen type 1 in both mAAA and fAAA. Alpha-smooth muscle actin (-SMA)-positive VSMCs were also reduced in mAAA and fAAA, but FAP was notably elevated, and robustly in fAAA. FAP-positive fibroblasts in fAAA exhibited increased expression of fibrosis markers, suggesting a unique pro-fibrotic phenotype. Conclusion: Our study reveals a sex-based difference in AAA tissue, with elevated fibrosis markers and increased FAP levels in females, suggesting its significant role in disease progression. These findings underscore the potential of FAP as a unique tissue biomarker for AAAs and warrants further investigation into novel targeted therapies that aim to stabilize AAAs, particularly in female patients.
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BibTeX
@misc{elizondobenedetto2026sexbased,
title = {{Sex-based differences in fibrosis markers in human abdominal aortic aneurysms}},
author = {Santiago Elizondo-Benedetto and Ryan Wahidi and Batool Arif and Brigida Rusconi and Maxwell C. Braasch and Dina Ibrahim and Mohamed S. Zaghloul and Omar Soltan and Noah Engles and Ibrahim Kuziez and J. Westley Ohman and Luis A. Sanchez and Mohamed A. Zayed},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.23.761467},
url = {https://www.biorxiv.org/content/10.64898/2026.10.23.761467v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Sex-based differences in fibrosis markers in human abdominal aortic aneurysms
AU - Santiago Elizondo-Benedetto
AU - Ryan Wahidi
AU - Batool Arif
AU - Brigida Rusconi
AU - Maxwell C. Braasch
AU - Dina Ibrahim
AU - Mohamed S. Zaghloul
AU - Omar Soltan
AU - Noah Engles
AU - Ibrahim Kuziez
AU - J. Westley Ohman
AU - Luis A. Sanchez
AU - Mohamed A. Zayed
PY - 2026
DA - 2026/10/23
PB - bioRxiv
DO - 10.64898/2026.10.23.761467
UR - https://www.biorxiv.org/content/10.64898/2026.10.23.761467v1
AB - Background: Abdominal aortic aneurysms (AAA) are a complex degenerative vascular disease. The role of fibrosis in AAA progression is unclear. Our study evaluated the impact of fibroblast activation protein (FAP), collagen, and vimentin on AAA fibrosis and progression. We hypothesized that FAP may influence fibrosis and disease severity in AAA, with potential sex-specific differences. Study Design: Multi-centered transcriptomic analysis of aortic samples from 15 human AAA and 5 non-AAA was performed to evaluate cell-specific fibrosis gene expression profiles. Histopathological and molecular analysis of 26 male and female AAA samples (mAAA and fAAA) and 29 male and female normal abdominal aortas (mNAA and fNAA) was performed to assess whole-tissue fibrosis markers and signaling. Results: Single-cell RNA sequencing (scRNA-seq) analysis identified eight major cell clusters with distinct sex-based distributions. Although vascular smooth muscle cells (VSMCs) and fibroblast clusters had reduced counts in both male and female AAAs, they more highly expressed FAP and COL1A1 genes, particularly in females. Whole-tissue analysis demonstrated elevated extracellular matrix deposits with markedly increased collagen type 1 in both mAAA and fAAA. Alpha-smooth muscle actin (-SMA)-positive VSMCs were also reduced in mAAA and fAAA, but FAP was notably elevated, and robustly in fAAA. FAP-positive fibroblasts in fAAA exhibited increased expression of fibrosis markers, suggesting a unique pro-fibrotic phenotype. Conclusion: Our study reveals a sex-based difference in AAA tissue, with elevated fibrosis markers and increased FAP levels in females, suggesting its significant role in disease progression. These findings underscore the potential of FAP as a unique tissue biomarker for AAAs and warrants further investigation into novel targeted therapies that aim to stabilize AAAs, particularly in female patients.
SN - 2692-8205
ER -