Size-dependent interactions between calciprotein particles and vascular endothelium
Zeping Zhang1,2, Xinyue Wang1,2, Caihao Huang1,3
1Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China.
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View abstract on PubMed
Small calciprotein particles (CPPs) disrupt the vascular endothelial barrier by widening gaps between cells, while larger CPPs are internalized. This size-dependent interaction impacts vascular health and nanoparticle design.
Area of Science:
- Nanomedicine and Vascular Biology
- Biomaterials Science
- Cellular and Molecular Physiology
Background:
- Mechanisms of nanoparticle-endothelial cell interactions are poorly understood, hindering optimal nanoparticle design for clinical use.
- Vascular endothelial barrier integrity is critical for systemic health, and its disruption can lead to pathological conditions like medial calcification.
- Calciprotein particles (CPPs) are implicated in vascular calcification, but their specific interactions with endothelial cells require elucidation.
Purpose of the Study:
- To investigate the size-dependent interactions between calciprotein particles (CPPs) and endothelial cells (ECs).
- To elucidate the impact of CPP size on endothelial barrier function and integrity.
- To inform the design of nanoparticles for therapeutic applications by understanding their vascular interactions.
Main Methods:
- Synthesized small (S-CPP1, <50 nm) and large (L-CPP1, 50-100 nm) calciprotein particles (CPPs) with distinct morphologies.
- Utilized a rat model of chronic kidney disease (CKD) induced by 5/6 nephrectomy.
- Assessed endothelial permeability and cell morphology using immunofluorescence microscopy and quantified intercellular gap changes.
Main Results:
- Small CPP1 (S-CPP1) significantly increased endothelial permeability at tested concentrations, disrupting the endothelial barrier integrity.
- S-CPP1 induced irregular endothelial cell morphology and widened intercellular gaps, suggesting disruption of VE-cadherin junctions.
- Large CPP1 (L-CPP1) was internalized by endothelial cells via endocytosis, showing size-specific uptake mechanisms.
Conclusions:
- The interaction between CPPs and the vascular endothelium is critically dependent on particle size.
- Small CPPs pose a greater risk to endothelial barrier integrity, potentially contributing to medial calcification.
- Understanding these size-dependent interactions is crucial for developing safer and more effective nanoparticle-based therapies.
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