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Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation - implications in atherosclerosis.
da Silva, Josiane Fernandes; Alves, Juliano V; Silva-Neto, Julio A; Costa, Rafael M; Neves, Karla B; Alves-Lopes, Rheure; Carmargo, Livia L; Rios, Francisco J; Montezano, Augusto C; Touyz, Rhian M; Tostes, Rita C.
Afiliação
  • da Silva JF; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo (FMRP-USP)- USP, Brazil.
  • Alves JV; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo (FMRP-USP)- USP, Brazil.
  • Silva-Neto JA; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo (FMRP-USP)- USP, Brazil.
  • Costa RM; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo (FMRP-USP)- USP, Brazil.
  • Neves KB; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Centre, University of Glasgow, Glasgow, U.K.
  • Alves-Lopes R; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Centre, University of Glasgow, Glasgow, U.K.
  • Carmargo LL; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Centre, University of Glasgow, Glasgow, U.K.
  • Rios FJ; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Centre, University of Glasgow, Glasgow, U.K.
  • Montezano AC; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Centre, University of Glasgow, Glasgow, U.K.
  • Touyz RM; Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Centre, University of Glasgow, Glasgow, U.K.
  • Tostes RC; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo (FMRP-USP)- USP, Brazil.
Clin Sci (Lond) ; 135(15): 1845-1858, 2021 08 13.
Article em En | MEDLINE | ID: mdl-34269800
OBJECTIVE: The mechanisms involved in NOX5 activation in atherosclerotic processes are not completely understood. The present study tested the hypothesis that lysophosphatidylcholine (LPC), a proatherogenic component of oxLDL, induces endothelial calcium influx, which drives NOX5-dependent reactive oxygen species (ROS) production, oxidative stress, and endothelial cell dysfunction. APPROACH: Human aortic endothelial cells (HAEC) were stimulated with LPC (10-5 M, for different time points). Pharmacological inhibition of NOX5 (Melittin, 10-7 M) and NOX5 gene silencing (siRNA) was used to determine the role of NOX5-dependent ROS production in endothelial oxidative stress induced by LPC. ROS production was determined by lucigenin assay and electron paramagnetic spectroscopy (EPR), calcium transients by Fluo4 fluorimetry, and NOX5 activity and protein expression by pharmacological assays and immunoblotting, respectively. RESULTS: LPC increased ROS generation in endothelial cells at short (15 min) and long (4 h) stimulation times. LPC-induced ROS was abolished by a selective NOX5 inhibitor and by NOX5 siRNA. NOX1/4 dual inhibition and selective NOX1 inhibition only decreased ROS generation at 4 h. LPC increased HAEC intracellular calcium, important for NOX5 activation, and this was blocked by nifedipine and thapsigargin. Bapta-AM, selective Ca2+ chelator, prevented LPC-induced ROS production. NOX5 knockdown decreased LPC-induced ICAM-1 mRNA expression and monocyte adhesion to endothelial cells. CONCLUSION: These results suggest that NOX5, by mechanisms linked to increased intracellular calcium, is key to early LPC-induced endothelial oxidative stress and pro-inflammatory processes. Since these are essential events in the formation and progression of atherosclerotic lesions, the present study highlights an important role for NOX5 in atherosclerosis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lisofosfatidilcolinas / Espécies Reativas de Oxigênio / Estresse Oxidativo / Células Endoteliais / Aterosclerose / NADPH Oxidase 5 Limite: Humans Idioma: En Revista: Clin Sci (Lond) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lisofosfatidilcolinas / Espécies Reativas de Oxigênio / Estresse Oxidativo / Células Endoteliais / Aterosclerose / NADPH Oxidase 5 Limite: Humans Idioma: En Revista: Clin Sci (Lond) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido