Ultrastructural changes in endothelium during apoptosis indicate low microembolic potential.
BACKGROUND
Apoptotic endothelium has been suggested to have microthrombotic and microembolic potential. While some describe pro-coagulant activities and platelet binding, others demonstrate maintained fibrinolytic protein and anti-platelet aggregatory activity. Canalicular fragmentation is unique to apoptotic endothelium and is suggested to facilitate size reduction of apoptotic cells to reduce microembolic potential. Despite the potential importance of apoptotic microemboli, there are no reports characterizing changes in cell size and shape during endothelial apoptosis.


METHODS
Here, we describe transmission and scanning electron microscopic studies of apoptotic endothelium and compare changes seen with apoptotic HL-60 cells incapable of canalicular fragmentation.


RESULTS
We demonstrate reduced endothelial size (p<0.05) with progressive apoptosis relative to apoptotic HL-60 cells. Mechanical stress accelerated size reduction of apoptotic endothelium(P< 0.01) but did not affect the size of apoptotic HL-60 cells. Mechanical stress also increased circularity in apoptotic endothelium (p<0.01), suggested to facilitate passage through small vessels. Earlier work indicated that canaliculi form through plasma membrane invagination, but we report fusion of small vesicles contributing to canalicular growth, while canaliculi fuse to form large vacuoles and also dilate at late stages of apoptosis.


CONCLUSIONS
These observations are consistent with the suggestion that endothelium is adapted to minimize microembolic potential and that canalicular fragmentation contributes to this.
Xu
Wei
W
Cellular and Molecular Pathology Research Unit, Department of Oral Pathology and Oral Medicine, University of Sydney, Westmead Centre for Oral Health S, Westmead, Australia.
Boadle
Ross
R
Dear
Levina
L
Cvejic
Mara
M
Emmanuel
Catherine
C
Zoellner
Hans
H
D017209:Apoptosis; D002462:Cell Membrane / Q000648:ultrastructure; D048429:Cell Size; D022162:Cytoplasmic Vesicles / Q000648:ultrastructure; D004617:Embolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000648:ultrastructure*; D018922:HL-60 Cells; D006801:Humans; D008833:Microcirculation; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000166:cytology; D014617:Vacuoles / Q000648:ultrastructure