Canalicular Fragmentation of Apoptotic Human Endothelial Cells

Abstract

Apoptosis of endothelial cells (EC) is responsible for the removal of blood vessels during vascular remodelling. Cultured human umbilical vein EC (HUVEC) undergo apoptosis if deprived of either serum or adhesion. Apoptotic HUVEC rapidly loose adhesion and in this paper we describe the ultrastructure of detached apoptotic HWEC and human microvascular EC (HMEC). These cells displayed the formation of apoptotic bodies, nuclear condensation and nuclear fragmentation typical of apoptosis in other cell types. Ultrastructural changes occurred in parallel with the internucleosomal DNA cleavage characteristic of apoptosis. An important difference between apoptotic HWEC and other reported cells was the formation of vesicle-like canalicular structures confluent with the plasma membrane surface. These structures formed an interconnecting network throughout the apoptotic cell. Apoptotic HMEC also displayed this canalicular pattern. Continuity of the plasma membrane surface of apoptotic EC with these canaliculi was established using colloidal gold particles. Canalicularisation seemed to increase the mechanical fragility of apoptotic EC, facilitating the fragmentation of apoptotic cells to very small particles. EC are comparatively large, so that EC detached during trauma could act as potentially dangerous micro-thrombi. Since detached EC become apoptotic, it is suggested that the canalicular fragmentation represents an EC adaptation to reduce the micro-embolic potential of apoptotic EC.