Hypoxia worsens the impact of intracellular triglyceride accumulation promoted by electronegative low-density lipoprotein in cardiomyocytes by impairing perilipin 5 upregulation

Elena Revuelta-López, Roi Cal, Josep Julve, Anna Rull, Maria Martínez-Bujidos, Montserrat Perez-Cuellar, Jordi Ordoñez-Llanos, Lina Badimon, Jose Luis Sanchez-Quesada, Vicenta Llorente-Cortés

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

© 2015 Elsevier Ltd. All rights reserved. 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(+)], LDL(-), and LDL(+) enriched in non-esterified fatty acids (NEFA) by phospholipase A<inf>2</inf> (PLA<inf>2</inf>)-mediated lipolysis [PLA<inf>2</inf>-LDL(+)] or by NEFA loading [NEFA-LDL(+)] under normoxia or hypoxia. LDL(-), PLA<inf>2</inf>-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<inf>2</inf>-LDL(+) and NEFA-LDL(+) in normoxic cardiomyocytes. Hypoxia enhanced the effect of LDL(-), PLA<inf>2</inf>-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<inf>2</inf>-LDL(+) and NEFA-LDL(+) have an increased production of reactive oxygen species (ROS). By treating hypoxic cardiomyocytes with WY-14643 (PPARα 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.
Original languageEnglish
Pages (from-to)257-267
JournalInternational Journal of Biochemistry and Cell Biology
Volume65
DOIs
Publication statusPublished - 29 Jun 2015

Keywords

  • Cardiomyopathy
  • Electronegative LDL
  • HL-1 cardiomyocytes
  • Nonesterified fatty acids
  • Perilipin 5a

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