Oxidized LDL attenuates protective autophagy and induces apoptotic cell death of endothelial cells: Role of oxidative stress and LOX-1 receptor expression

Vincenzo Mollace, Micaela Gliozzi, Vincenzo Musolino, Cristina Carresi, Saverio Muscoli, Rocco Mollace, Annamaria Tavernese, Santo Gratteri, Ernesto Palma, Chiara Morabito, Cristiana Vitale, Carolina Muscoli, Massimo Fini, Francesco Romeo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)152-158
Number of pages7
JournalInternational Journal of Cardiology
Volume184
Issue number1
DOIs
Publication statusPublished - 2015

Keywords

  • LOX-1
  • Oxidative stress
  • Oxidized-LDL
  • Protective autophagy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

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    Mollace, V., Gliozzi, M., Musolino, V., Carresi, C., Muscoli, S., Mollace, R., Tavernese, A., Gratteri, S., Palma, E., Morabito, C., Vitale, C., Muscoli, C., Fini, M., & Romeo, F. (2015). Oxidized LDL attenuates protective autophagy and induces apoptotic cell death of endothelial cells: Role of oxidative stress and LOX-1 receptor expression. International Journal of Cardiology, 184(1), 152-158. https://doi.org/10.1016/j.ijcard.2015.02.007