Endothelial progenitor cell down-regulation in a mouse model of Kawasaki disease
Jun-Feng Liu1, Zhong-Dong Du, Zhi Chen
1Department of Pediatrics, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
Insights
Kawasaki disease (KD) coronary artery lesions are linked to a significant decrease in endothelial progenitor cells (EPCs). Impaired EPC function and reduced numbers contribute to poor vascular repair in KD.
Area of Science:
- Pediatric cardiology
- Vascular biology
- Immunology
Background:
- Cardiovascular complications are a significant concern in pediatric Kawasaki disease (KD).
- Endothelial progenitor cells (EPCs) are implicated in coronary artery lesions in KD.
- Long-term observational data on EPCs in KD progression are limited.
Purpose of the Study:
- To investigate the role of endothelial progenitor cells (EPCs) in the development of coronary artery lesions in an experimental model of Kawasaki disease (KD).
- To determine if coronary artery lesions in KD are associated with a down-regulation of EPCs.
Main Methods:
- An experimental model of KD was induced in C57BL/6 mice using Lactobacillus casei cell wall extract (LCWE).
- Circulating EPCs were quantified using flow cytometry (CD34+/Flk-1+/CD45-).
- In vitro functional analyses assessed EPC proliferation, adhesion, and migration.
Main Results:
- The KD model successfully replicated coronary artery lesions observed in human KD patients.
- Significant reductions in circulating EPC numbers were observed in KD groups compared to controls.
- Impaired proliferative, adhesive, and migratory capacities of EPCs were noted in KD models.
Conclusions:
- Coronary artery lesions in KD are associated with impaired vascular repair mechanisms.
- Excessive consumption and functional deficits of EPCs contribute to the pathogenesis of KD-associated vascular injury.
- Bone marrow EPCs and their precursors exhibit functional impairment in the context of KD.
Background:
Cardiovascular complications of Kawasaki disease (KD) are a common cause of heart disease in pediatric populations. Previous studies have suggested a role for endothelial progenitor cells (EPCs) in coronary artery lesions associated with KD. However, long-term observations of EPCs during the natural progression of this disorder are lacking. Using an experimental model of KD, we aimed to determine whether the coronary artery lesions are associated with down-regulation of EPCs.
Methods:
To induce KD, C57BL/6 mice were administered an intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE; phosphate buffered saline used as control vehicle). Study groups included: group A (14 days following LCWE injection), group B (56 days following LCWE injection) and group C (controls). Numbers of circulating EPCs (positively staining for both CD34 and Flk-1 while staining negative for CD45) were evaluated using flow cytometry. Bone marrow mononuclear cells were cultured in vitro to expand EPCs for functional analysis. In vitro EPC proliferation, adhesion and migration were assessed.
Results:
The model was shown to exhibit similar coronary artery lesions to KD patients with coronary aneurysms. Numbers of circulating EPCs decreased significantly in the KD models (groups A and B) compared to controls ((0.017 ± 0.008)% vs. (0.028 ± 0.007)%, P < 0.05 and (0.016 ± 0.007)% vs. (0.028 ± 0.007)%, P < 0.05). Proliferative, adhesive and migratory properties of EPCs were markedly impaired in groups A and B.
Conclusion:
Coronary artery lesions in KD occur as a consequence of impaired vascular injury repair, resulting from excess consumption of EPCs together with a functional impairment of bone marrow EPCs and their precursors.
