Related Experiment Video
Updated: Jan 15, 2026
Murine Model of Thoracic Aortic Dissection Induced by Oral β-Aminopropionitrile and Subcutaneous Angiotensin II Infusion
Published on: May 16, 2025
Inhibition of S100A9 Improves Aortic Dissection in Association With Mitochondrial Function Enhancement
Keyu Zhang1,2,3, Linman Li4, Yiying Zhang5
1Cardiovascular Disease Laboratory, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
Insights
S100 calcium-binding protein A9 (S100A9) is elevated in aortic dissection (AD). Inhibiting S100A9 protects against AD in mice and may offer a new therapeutic strategy for this cardiovascular emergency.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pathophysiology
Background:
- Aortic dissection (AD) is a life-threatening cardiovascular condition with poorly understood mechanisms.
- S100 calcium-binding protein A9 (S100A9) is investigated as a potential therapeutic target for AD.
Purpose of the Study:
- To investigate the role of S100A9 in the pathogenesis of aortic dissection.
- To explore the therapeutic potential of S100A9 inhibition for AD.
Main Methods:
- Proteomic analysis of human aortic tissues.
- Aortic dissection model in S100A9 knockout mice.
- Single-cell RNA sequencing to analyze cellular and mitochondrial changes.
- In vitro studies on mitochondrial function in THP-1 cells.
Main Results:
- S100A9 was significantly upregulated in AD tissues.
- S100A9 knockout mice showed protection against AD-induced mortality and aortic dilation.
- S100A9 inhibition activated mitochondrial oxidative phosphorylation and upregulated mtDNA expression.
- S100A9 reduced mitochondrial membrane potential and increased oxidative stress in vitro.
Conclusions:
- S100A9 plays a role in the pathogenesis of aortic dissection.
- Targeting S100A9 presents a promising therapeutic avenue for AD treatment.
Background:
Aortic dissection (AD) is a high-mortality cardiovascular emergency with unclear pathophysiological mechanisms. This study investigated S100 calcium-binding protein A9 (S100A9) as a therapeutic target for AD and explored its underlying mechanisms.
Methods:
Proteomic analysis compared aortic tissues from patients with acute type A and matched non-dissected vascular tissues from the same patients. An AD model was induced in wild-type and S100A9 knockout mice via β-aminopropionitrile (BAPN). Survival, aortic diameter, and S100A9 expression were quantified. Furthermore, single-cell RNA sequencing was used to analyze cell populations and mitochondrial pathways in AD mice treated with an S100A9 inhibitor. Finally, the effect of S100A9 on mitochondrial function was investigated in Tohoku Hospital Pediatrics-1 (THP-1) cells.
Results:
Proteomics identified that S100A9 is significantly upregulated in AD tissue. Furthermore, S100a9 knockout (S100a9 KO) mice conferred protection against AD-induced mortality and aortic dilation. Single-cell RNA analysis revealed that S100A9 is predominantly expressed within the granulocyte population. S100A9 inhibition activated mitochondrial oxidative phosphorylation pathways and upregulated mtDNA-encoded gene expression. Human tissue mRNA levels confirmed decreased mtDNA in AD. Moreover, recombinant human S100A9 and angiotensin-II treatment in THP-1 cells reduced mitochondrial membrane potential and increased oxidative stress.
Conclusions:
S100A9 is a potential contributor to AD pathogenesis. Inhibition of S100A9 might be a promising therapeutic target for AD.
