Low density lipoprotein receptor-related protein 1 expression correlates with cholesteryl ester accumulation in the myocardium of ischemic cardiomyopathy patients
Cal, Roi (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Juan-Babot, Oriol (Institut d'Investigació Biomèdica Sant Pau)
Brossa, Vicenç (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Roura, Santiago (Institut Germans Trias i Pujol)
Gálvez-Montón, Carolina (Institut Germans Trias i Pujol)
Portoles, Manolo (Hospital Universitari i Politècnic La Fe (València))
Rivera, Miguel (Hospital Universitari i Politècnic La Fe (València))
Cinca, Juan (Institut d'Investigació Biomèdica Sant Pau)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Llorente-Cortés, Vicenta (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Data:	2012
Resum:	Our hypothesis was that overexpression of certain lipoprotein receptors might be related to lipid accumulation in the human ischemic myocardium. Intramyocardial lipid overload contributes to contractile dysfunction and arrhythmias in cardiomyopathy. Thus, the purpose of this study was to assess the effect of hypercholesterolemic LDL and hypertrigliceridemic VLDL dose on LRP1 expression in cardiomyocytes, as well as the potential correlation between LRP1 expression and neutral lipid accumulation in the left ventricle tissue from ischemic cardiomyopathy patients. Cell culture experiments include control and LRP1-deficient cardiomyocytes exposed to lipoproteins under normoxic and hypoxic conditions. Explanted hearts from 18 ICM patients and eight non-diseased hearts (CNT) were included. Low density lipoprotein receptor-related protein 1 (LRP1), very low density lipoprotein receptor (VLDLR) and low density lipoprotein receptor (LDLR) expression was analyzed by real time PCR and Western blotting. Cholesteryl ester (CE), triglyceride (TG) and free cholesterol (FC) content was assess by thin layer chromatography following lipid extraction. Western blotting experiments showed that protein levels of LRP1, VLDLR and HIF-1α were significantly upregulated in ischemic hearts. Immunohistochemistry and confocal microscopy analysis showed that LRP1 and HIF-1α were upregulated in cardiomyocytes of ICM patients. In vitro studies showed that VLDL, LDL and hypoxia exerted an upregulatory effect on LRP1 expression and that LRP1 played a major role in cholesteryl ester accumulation from lipoproteins in cardiomyocytes. Myocardial CE accumulation strongly correlated with LRP1 levels in ischemic hearts. Taken together, our results suggest that LRP1 upregulation is key for myocardial cholesterol ester accumulation in ischemic human hearts and that LRP1 may be a target to prevent the deleterious effects of myocardial cholesterol accumulation in ischemic cardiomyopathy. © 2012 Cal et al. ; licensee BioMed Central Ltd.
Ajuts:	Ministerio de Sanidad y Consumo RD06/0003/1001 Ministerio de Ciencia e Innovación PI11/00747 Fundació la Marató de TV3 080110
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	HIF-1α myocardial lipid accumulation ; LRP1, VLDLR ; Ischemic cardiomyopathy
Publicat a:	Journal of translational medicine, Vol. 10 Núm. 1 (august 2012) , p. 160, ISSN 1479-5876

DOI: 10.1186/1479-5876-10-160
PMID: 22873206

11 p, 683.2 KB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
Articles > Articles de recerca
Articles > Articles publicats