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Interleukin-17F Induces Ischemic Injury in Aged Mice by Causing Endothelial Cells' Senescence and Dysfunction
Minghong Chen1,2,3,4, Junyu Chen1,2,3,4, Yu Liu3,5
1Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Summary
Elevated Interleukin-17F (IL-17F) is linked to peripheral arterial disease (PAD) severity and poor outcomes. Neutralizing IL-17F improved blood flow and repair in aged mice, suggesting a potential therapy for PAD.
Area of Science:
- Cardiovascular Research
- Immunology
- Aging Biology
Background:
- Peripheral arterial disease (PAD) is a common circulatory disorder, particularly in aging populations.
- Interleukin-17 (IL-17) cytokines, including IL-17A and IL-17F, play roles in inflammation and vascular health.
- The specific role of IL-17F in PAD pathogenesis and neovascularization remains incompletely understood.
Purpose of the Study:
- To investigate the association between plasma IL-17A and IL-17F levels and PAD.
- To explore the functional role of IL-17F in neovascularization within a preclinical model of PAD in aged mice.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) to quantify plasma IL-17A and IL-17F levels.
- Spearman correlation analysis to assess relationships between IL-17F and PAD severity/outcomes.
- In vitro studies on endothelial cells (ECs) under simulated ischemic conditions.
- In vivo studies using aged mice with induced hindlimb ischemia, including IL-17F neutralization, Doppler imaging, functional scoring, histology, and Micro-CT.
Main Results:
- Plasma IL-17F levels were elevated in aged PAD patients and mice, correlating positively with PAD severity, onset risk, and cardiovascular outcomes.
- IL-17F induced dose-dependent EC senescence and dysfunction in vitro.
- Neutralization of IL-17F in aged mice significantly enhanced blood flow recovery, reduced ischemia, improved motor function, and promoted muscle regeneration.
- IL-17F neutralization promoted neovascularization and reduced EC senescence in ischemic hindlimb muscles.
Conclusions:
- Higher plasma IL-17F levels are significantly associated with increased PAD severity, onset risk, and adverse cardiovascular outcomes.
- Targeting IL-17F demonstrates therapeutic potential by enhancing post-ischemic neovascularization and repair in aged individuals.
- Neutralization of IL-17F represents a promising therapeutic strategy for elderly patients with PAD.
