Hypoxia worsens the impact of intracellular triglyceride accumulation promoted by electronegative low-density lipoprotein in cardiomyocytes by impairing perilipin 5 upregulation
Por:
Revuelta-Lopez, E, Cal, R, Julve, J, Rull, A, Martinez-Bujidos, M, Perez-Cuellar, M, Ordonez-Llanos, J, Badimon, L, Sanchez-Quesada, JL, Llorente-Cortes, V
Publicada:
1 ago 2015
Resumen:
Plasma lipoproteins are a source of lipids for the heart, and the proportion of electronegative low density lipoprotein [LDL(-)] is elevated in cardiometabolic diseases. Perilipin 5 (Plin5) is a crucial protein for lipid droplet management in the heart. Our aim was to assess the effect of LDL(-) on intracellular lipid content and Plin5 levels in cardiomyocytes and to determine whether these effects were influenced by hypoxia. HL-1 cardiomyocytes were exposed to native LDL [LDL(+)1, LDL(-), and LDL(+) enriched in non-esterified fatty acids (NEFA) by phospholipase A(2) (PLA(2))-mediated lipolysis [PLA(2)-LDL(+)] or by NEFA loading [NEFA-LDL(+)] under normoxia or hypoxia. LDL(-), PLA(2)-LDL(+) and NEFA-LDL(+) raised the intracellular NEFA and triglyceride (TG) content of normoxic cardiomyocytes. Plin5 was moderately upregulated by LDL(+) but more highly upregulated by LDL(-), PLA(2)-LDL(+) and NEFA-LDL(+) in normoxic cardiomyocytes. Hypoxia enhanced the effect of LDL(-), PLA(2)-LDL(+) and NEFA-LDL(+) on intracellular TG and NEFA concentrations but, in contrast, counteracted the upregulatory effect of these LDLs on Plin5. Fluorescence microscopy experiments showed that hypoxic cardiomyocytes exposed to LDL(-), PLA(2)-LDL(+) and NEFA-LDL(+) have an increased production of reactive oxygen species (ROS). By treating hypoxic cardiomyocytes with WY-14643 (PPARoe agonist), Plin5 remained high. In this situation, LDL(-) failed to enhance intracellular NEFA concentration and ROS production. In conclusion, these results show that Plin5 deficiency in hypoxic cardiomyocytes exposed to LDL(-) dramatically increases the levels of unpacked NEFA and ROS. (C) 2015 Elsevier Ltd. All rights reserved.
Filiaciones:
Revuelta-Lopez, E:
Hosp Santa Creu & Sant Pau, CSIC ICCC, Cardiovasc Res Ctr, IIB St Pau, Barcelona 08036, Spain
Cal, R:
Hosp Santa Creu & Sant Pau, CSIC ICCC, Cardiovasc Res Ctr, IIB St Pau, Barcelona 08036, Spain
Julve, J:
Hosp Santa Creu & Sant Pau, Inst Invest, Metab Basis Cardiovasc Risk, IIB St Pau, Barcelona 08036, Spain
CIBERDEM, CIBER Diabet & Enfermedades Metabol Asociadas, Barcelona, Spain
Rull, A:
Hosp Santa Creu & Sant Pau, Inst Invest, Cardiovasc Biochem Grp, IIB St Pau, Barcelona 08036, Spain
Martinez-Bujidos, M:
Hosp Santa Creu & Sant Pau, Inst Invest, Cardiovasc Biochem Grp, IIB St Pau, Barcelona 08036, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, E-08193 Barcelona, Spain
Perez-Cuellar, M:
Hosp Santa Creu & Sant Pau, Inst Invest, Cardiovasc Biochem Grp, IIB St Pau, Barcelona 08036, Spain
Ordonez-Llanos, J:
Hosp Santa Creu & Sant Pau, Inst Invest, Cardiovasc Biochem Grp, IIB St Pau, Barcelona 08036, Spain
Univ Autonoma Barcelona, Dept Bioquim & Biol Mol, E-08193 Barcelona, Spain
Badimon, L:
Hosp Santa Creu & Sant Pau, CSIC ICCC, Cardiovasc Res Ctr, IIB St Pau, Barcelona 08036, Spain
Sanchez-Quesada, JL:
Hosp Santa Creu & Sant Pau, Inst Invest, Cardiovasc Biochem Grp, IIB St Pau, Barcelona 08036, Spain
Llorente-Cortes, V:
Hosp Santa Creu & Sant Pau, CSIC ICCC, Cardiovasc Res Ctr, IIB St Pau, Barcelona 08036, Spain
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