High-lipid treatment regulates atherosclerotic development and aortic
endothelial cells apoptosis via FOXO3 activation
Abstract
Background:Endothelial cell apoptosis plays an important role
in the progression of atherosclerosis. Oxidized low density lipoprotein
(Ox-LDL) induces endothelial cell apoptosis through multiple signaling
pathways. We investigated the role of FOXO3 activation in the
development of atherosclerosis and ox-LDL induced mouse aortic
endothelial cell (MAEC) apoptosis. Methods: In vivo, ApoE-/-
mice atherosclerosis model was induced by high fat feeding and the FOXO3
expression in aorta endothelium were measured by IHC. In vitro,MAECs
were induced with ox-LDL to establish an atherosclerosis model. The cell
viability and apoptosis were measured by MTT and Hoechst 33342 staining.
The FOXO3 expression was measured by Q-PCR. Then we constructed two
plasmids: the interference vector for FOXO3 and the expression vector
for FOXO3. The effects of the two plasmids on MAECs were evaluated.
Results: The results of in vivo experiments showed that
FOXO3 activation in mouse aortic endothelium was associated with
atherosclerosis (ApoE −/− mice model of
atherosclerosis). Furthermore, ox-LDL triggers MAEC apoptosis. FOXO3
activation was associated with Ox-LDL-induced MAEC apoptosis. RNA
interference-mediated reduction of FOXO3 expression blunted
Ox-LDL-induced MAEC apoptosis. In contrast, overexpression of FOXO3
promoted Ox-LDL-induced MAEC apoptosis. Conclusions: FOXO3
activation is therefore involved in the development of atherosclerosis
and MAEC apoptosis.