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A relationship between apoptosis and flow during programmed capillary regression is revealed by vital analysis
1Skirball Institute for Biomolecular Medicine, Cell Biology Department, New York University Medical Center, New York, NY 10016, USA.
Summary
Capillary regression involves programmed cell death of vascular endothelial cells (VECs). Macrophages initiate VEC apoptosis, blocking blood flow and leading to further cell death in capillaries.
Area of Science:
- Vascular biology
- Cell biology
- Developmental biology
Background:
- Capillary regression involves programmed vascular endothelial cell (VEC) death.
- Previous models proposed macrophage-dependent and blood flow cessation-dependent VEC death.
- A combined model suggested initial VEC apoptosis by macrophages leads to flow cessation and subsequent VEC apoptosis.
Purpose of the Study:
- To test the proposed model of capillary regression.
- To determine the fate of capillary segments and individual cells during regression in vivo.
- To elucidate the sequence of events and causal relationships in capillary regression.
Main Methods:
- Developed a novel method combining vital and histological analyses.
- Applied this technique to study capillary regression in vivo.
- Quantitatively analyzed plasma flow and VEC apoptosis.
Main Results:
- Identified initial apoptosis of a single VEC in flowing capillaries (initiating apoptosis).
- Observed that dying VECs restricted capillary lumen, causing flow cessation.
- Found synchronous VEC apoptosis (secondary apoptosis) following flow cessation.
- Revealed a reciprocal relationship between plasma flow and VEC apoptosis.
Conclusions:
- The study supports a model where macrophages induce initial VEC apoptosis.
- This initial apoptosis leads to blood flow cessation, causing secondary VEC apoptosis.
- Capillary regression is a process initiated by VEC apoptosis and exacerbated by flow cessation.