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The HCG11/QKI5 Axis Regulates Endothelial Angiogenic Adaptation During Chronic Cerebral Hypoperfusion
Xueqiao Jiao1, Rui Li2, Lulan Li1
1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Insights
The HCG11/QKI5 axis regulates blood vessel repair in chronic cerebral hypoperfusion, a condition linked to intracranial atherosclerotic stenosis (ICAS). Its progressive failure impairs vascular compensation, suggesting a therapeutic target for ICAS.
Area of Science:
- Neuroscience
- Vascular Biology
- Molecular Medicine
Background:
- Chronic cerebral hypoperfusion exacerbates intracranial atherosclerotic stenosis (ICAS) progression and ischemic risk.
- Endothelial angiogenic adaptation initially compensates for reduced blood flow but fails as ICAS advances.
- The HCG11/QKI5 axis's role in this adaptive failure remains unclear.
Purpose of the Study:
- To investigate the HCG11/QKI5 axis as a regulatory node in cerebral hypoperfusion.
- To explore its therapeutic potential for mitigating ICAS progression.
Main Methods:
- Compared hypoxia- and angiogenesis-related biomarkers in asymptomatic vs. symptomatic ICAS patients.
- Assessed endothelial function in vitro using oxygen-glucose deprivation with HCG11 overexpression or QKI5 knockdown.
- Evaluated in vivo temporal changes in a rat model of chronic cerebral hypoperfusion.
Main Results:
- Asymptomatic ICAS patients showed elevated pro-angiogenic factors, while symptomatic patients had reduced levels, indicating impaired vascular compensation.
- HCG11 overexpression boosted endothelial proliferation and tube formation; QKI5 silencing had the opposite effect, modulating HIF-1α/VEGF signaling.
- In vivo, early hypoperfusion activated QKI5 and angiogenic pathways, which declined with sustained hypoperfusion.
Conclusions:
- Progressive failure of the HCG11/QKI5-mediated angiogenic program may cause endothelial adaptive failure in cerebral hypoperfusion.
- Targeting this RNA-regulatory axis offers a potential therapeutic strategy to preserve vascular compensation and reduce ICAS progression.
Aims:
Chronic cerebral hypoperfusion drives the progression of intracranial atherosclerotic stenosis (ICAS) and increases ischemic risk. Endothelial angiogenic adaptation initially preserves cerebral perfusion but deteriorates with disease progression. We investigated whether the HCG11/QKI5 axis represents a regulatory node with therapeutic potential in cerebral hypoperfusion.
Methods:
Circulating hypoxia- and angiogenesis-related biomarkers were compared between asymptomatic and symptomatic ICAS patients to reflect different progression stages. Endothelial function was assessed in oxygen-glucose deprivation models following HCG11 overexpression or QKI5 knockdown. A rat model of chronic cerebral hypoperfusion was used to evaluate temporal changes in vivo.
Results:
Pro-angiogenic factors were elevated in asymptomatic ICAS but reduced in symptomatic patients, indicating progressive impairment of vascular compensation. HCG11 overexpression enhanced endothelial proliferation and tube formation, whereas QKI5 silencing attenuated these responses. These effects were associated with modulation of HIF-1α/VEGF signaling. In vivo, early hypoperfusion activated QKI5 and angiogenic pathways, followed by a gradual decline during sustained hypoperfusion.
Conclusion:
Progressive attenuation of the HCG11/QKI5-mediated angiogenic program may underlie endothelial adaptive failure in cerebral hypoperfusion. Targeting this RNA-regulatory axis may represent a potential therapeutic strategy to preserve vascular compensation and mitigate disease progression in ICAS.
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