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Weibel-Palade Bodies Orchestrate Pericytes During Angiogenesis
Mélissande Cossutta1, Marie Darche1, Gilles Carpentier1
1From the CRRET laboratory, CNRS ERL 9215, University of Paris-Est Créteil (UPEC), France (M.C., M.D., G.C., C.H., M.P., F.R., B.V., M.-E.G., D.V., J.C., I.C.).
Arteriosclerosis, Thrombosis, and Vascular Biology
|July 19, 2019
Summary
Weibel-Palade bodies (WPBs) release angiopoietin-2 (Ang-2) during angiogenesis, which limits pericyte coverage of new vessels. This process is regulated by vascular endothelial growth factor (VEGF) signaling.
Area of Science:
- Endothelial cell biology
- Angiogenesis research
- Vascular development
Background:
- Weibel-Palade bodies (WPBs) are specialized organelles in endothelial cells (ECs) crucial for vascular repair and inflammation.
- WPBs contain von Willebrand factor (vWF) and angiopoietin-2 (Ang-2), a proangiogenic factor.
- The role of WPBs in angiogenesis and vessel stabilization requires further investigation.
Purpose of the Study:
- To investigate the role of WPBs in angiogenesis and vessel stabilization.
- To elucidate the regulation of WPB exocytosis and Ang-2 secretion during angiogenesis.
- To determine the impact of WPB function on pericyte coverage.
Main Methods:
- Quantitative analysis of WPB density in retinal vascular networks during development and neovascularization.
- In vitro studies using ECs to assess VEGF-induced WPB exocytosis and Ang-2 secretion.
- In vivo experiments involving anti-VEGF treatment and vWF knockout mice.
- Assessment of pericyte migration and coverage in response to WPB modulation.
Main Results:
- WPB density was lower at the angiogenic front compared to stable vessels.
- VEGF stimulation induced VEGFR-2-dependent WPB exocytosis and Ang-2 secretion.
- Blocking WPB exocytosis and Ang-2 secretion promoted pericyte migration.
- In vivo, anti-VEGF treatment increased WPB accumulation and pericyte coverage.
- In tumor models, WPB depletion increased angiogenesis and decreased pericyte coverage.
Conclusions:
- WPB exocytosis and Ang-2 secretion are regulated during angiogenesis.
- This regulation limits pericyte coverage of remodeling vessels by modulating Ang-1/Tie2 signaling.
- WPBs play a critical role in controlling vessel maturation and stability.
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