TY - JOUR
T1 - Oxidized LDL attenuates protective autophagy and induces apoptotic cell death of endothelial cells
T2 - Role of oxidative stress and LOX-1 receptor expression
AU - Mollace, Vincenzo
AU - Gliozzi, Micaela
AU - Musolino, Vincenzo
AU - Carresi, Cristina
AU - Muscoli, Saverio
AU - Mollace, Rocco
AU - Tavernese, Annamaria
AU - Gratteri, Santo
AU - Palma, Ernesto
AU - Morabito, Chiara
AU - Vitale, Cristiana
AU - Muscoli, Carolina
AU - Fini, Massimo
AU - Romeo, Francesco
PY - 2015
Y1 - 2015
N2 - Background: Overproduction of oxidized-low density lipoproteins (oxyLDLs) has been found to contribute in endothelial cell (EC) dysfunction thereby leading to atherosclerosis development and progression. In particular, oxyLDLs lead to apoptotic cell death of EC via oxidative stress production, mostly subsequent to the overexpression of the scavenger receptor LOX-1. Here, we hypothesize that LOX-1 expression in EC represents a crucial event which attenuates protective autophagic response, thereby enhancing programmed endothelial cell death. Methods and results: Bovine aortic endothelial cells (BAECs) in culturewere exposed to oxyLDL (1-100 μM). After 48 h incubation, oxyLDL produced pronounced malondialdehyde (MDA) elevation and apoptotic cell death of BAEC as detected by FACS analysis, an effect counteracted by antioxidant N-acetyl-cysteine (NAC) as well as by the NO-donor SNAP. OxyLDL-induced apoptotic cell death was also accompanied by reduced VEGF-dependent phosphorylation of constitutive NO synthase (cNOS) in BAEC and consistent attenuation of autophagic response as detected by the expression of Beclin-1 and LC3, two reliable biomarkers of autophagy. Moreover, silencing LOX-1 receptor significantly restored LC3 expression in oxyLDL-treated BAEC, thus suggesting a key role of LOX-1 overproduction in oxyLDL-induced endothelial dysfunction. Conclusions: OxyLDL leads to impaired NO generation and apoptotic cell death in BAECs. This effect occurs via the overexpression of LOX-1 and subsequent attenuation of protective autophagic response thereby contributing to the pathophysiology of oxyLDL-induced endothelial dysfunction which characterizes early stages of atherosclerotic process.
AB - Background: Overproduction of oxidized-low density lipoproteins (oxyLDLs) has been found to contribute in endothelial cell (EC) dysfunction thereby leading to atherosclerosis development and progression. In particular, oxyLDLs lead to apoptotic cell death of EC via oxidative stress production, mostly subsequent to the overexpression of the scavenger receptor LOX-1. Here, we hypothesize that LOX-1 expression in EC represents a crucial event which attenuates protective autophagic response, thereby enhancing programmed endothelial cell death. Methods and results: Bovine aortic endothelial cells (BAECs) in culturewere exposed to oxyLDL (1-100 μM). After 48 h incubation, oxyLDL produced pronounced malondialdehyde (MDA) elevation and apoptotic cell death of BAEC as detected by FACS analysis, an effect counteracted by antioxidant N-acetyl-cysteine (NAC) as well as by the NO-donor SNAP. OxyLDL-induced apoptotic cell death was also accompanied by reduced VEGF-dependent phosphorylation of constitutive NO synthase (cNOS) in BAEC and consistent attenuation of autophagic response as detected by the expression of Beclin-1 and LC3, two reliable biomarkers of autophagy. Moreover, silencing LOX-1 receptor significantly restored LC3 expression in oxyLDL-treated BAEC, thus suggesting a key role of LOX-1 overproduction in oxyLDL-induced endothelial dysfunction. Conclusions: OxyLDL leads to impaired NO generation and apoptotic cell death in BAECs. This effect occurs via the overexpression of LOX-1 and subsequent attenuation of protective autophagic response thereby contributing to the pathophysiology of oxyLDL-induced endothelial dysfunction which characterizes early stages of atherosclerotic process.
KW - LOX-1
KW - Oxidative stress
KW - Oxidized-LDL
KW - Protective autophagy
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U2 - 10.1016/j.ijcard.2015.02.007
DO - 10.1016/j.ijcard.2015.02.007
M3 - Article
C2 - 25703423
AN - SCOPUS:84933519314
VL - 184
SP - 152
EP - 158
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
IS - 1
ER -