RGD Reference Report - Low-density lipoprotein receptor-related protein 1 mediates hypoxia-induced very low density lipoprotein-cholesteryl ester uptake and accumulation in cardiomyocytes. - Rat Genome Database
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Low-density lipoprotein receptor-related protein 1 mediates hypoxia-induced very low density lipoprotein-cholesteryl ester uptake and accumulation in cardiomyocytes.

Authors: Cal, Roi  Castellano, José  Revuelta-López, Elena  Aledo, Rosa  Barriga, Montse  Farré, Jordi  Vilahur, Gemma  Nasarre, Laura  Hove-Madsen, Leif  Badimon, Lina  Llorente-Cortés, Vicenta 
Citation: Cal R, etal., Cardiovasc Res. 2012 Jun 1;94(3):469-79. doi: 10.1093/cvr/cvs136. Epub 2012 Mar 27.
RGD ID: 13800524
Pubmed: (View Article at PubMed) PMID:22454363
DOI: Full-text: DOI:10.1093/cvr/cvs136


AIMS: The myocardium accumulates intracellular lipids under ischaemic conditions, and myocardial fat deposition is closely associated with cardiac dysfunction. Our aims were to analyse the effect of hypoxia on low-density lipoprotein receptor-related protein 1 (LRP1) expression in neonatal rat ventricular myocytes (NRVM) and cardiac-derived HL-1 cells and the molecular mechanisms involved in this effect, to determine the role of LRP1 in the very low density lipoprotein (VLDL) uptake by hypoxic cardiomyocytes, and to study the effect of hypoxia on lipoprotein receptor expression and myocardial lipid profile in an in vivo porcine experimental model of acute myocardial infarction.
METHODS AND RESULTS: Thin-layer chromatography after lipid extraction showed that VLDL exposure leads to cholesteryl ester (CE) and triglyceride (TG) accumulation in a dose-dependent manner and that hypoxic conditions further increased VLDL-derived intracellular lipid accumulation in HL-1 cells. Knockdown of LRP1 through lentiviral-mediated interfering RNA specifically prevented hypoxia-induced VLDL-CE internalization in HL-1 cells and NRVM. Lipopolysaccharide (LPS)-induced LRP1 overexpression specifically increased VLDL-CE accumulation in NRVM. In addition, using double-radiolabelled [(3)H]CE-[(14)C]TG-VLDL, we found that LRP1 deficiency specifically prevented hypoxia-induced VLDL-[(3)H]CE uptake. Finally, in an in vivo porcine model of infarcted myocardium, ischaemic areas exhibited LRP1 protein up-regulation and intramyocardial CE overaccumulation.
CONCLUSION: Our results demonstrate that hypoxia increases LRP1 expression through HIF-1α and that LRP1 overexpression mediates hypoxia-induced VLDL-CE uptake and accumulation in cardiomyocytes.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Lrp1  (LDL receptor related protein 1)


Additional Information