Macrophages of genetically characterized familial hypercholesterolaemia patients show up-regulation of LDL-receptor-related proteins
Escate, Rafael (Institut d'Investigació Biomèdica Sant Pau)
Padró, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Borrell-Pages, Maria (Institut d'Investigació Biomèdica Sant Pau)
Suades, Rosa (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Aledo, Rosa (Institut d'Investigació Biomèdica Sant Pau)
Mata, Pedro (Foundation Jimenez Diaz)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	Familial hypercholesterolaemia (FH) is a major risk for premature coronary heart disease due to severe long-life exposure to high LDL levels. Accumulation of LDL in the vascular wall triggers atherosclerosis with activation of the innate immunity system. Here, we have investigated (i) gene expression of LDLR and LRPs in peripheral blood cells (PBLs) and in differentiated macrophages of young FH-patients; and (ii) whether macrophage from FH patients have a differential response when exposed to high levels of atherogenic LDL. PBLs in young heterozygous genetically characterized FH patients have higher expression of LRP5 and LRP6 than age-matched healthy controls or patients with secondary hypercholesterolaemia. LRP1 levels were similar among groups. In monocyte-derived macrophages (MACs), LRP5 and LRP1 transcript levels did not differ between FHs and controls in resting conditions, but when exposed to agLDL, FH-MAC showed a highly significant up-regulation of LRP5, while LRP1 was unaffected. PBL and MAC cells from FH patients had significantly lower LDLR expression than control cells, independently of the lipid-lowering therapy. Furthermore, exposure of FH-MAC to agLDL resulted in a reduced expression of CD163, scavenger receptor with anti-inflammatory and atheroprotective properties. In summary, our results show for first time that LRPs, active lipid-internalizing receptors, are up-regulated in innate immunity cells of young FH patients that have functional LDLR mutations. Additionally, their reduced CD163 expression indicates less atheroprotection. Both mechanisms may play a synergic effect on the onset of premature atherosclerosis in FH patients.
Grants:	Ministerio de Economía y Competitividad SAF2013-42962-R Ministerio de Economía y Competitividad PI13/02850 Ministerio de Economía y Competitividad RD12/0042/0027
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Atherosclerosis ; CD163 ; Familial hypercholesterolaemia ; Macrophages ; LRPs
Published in:	Journal of Cellular and Molecular Medicine, Vol. 21 Núm. 3 (january 2017) , p. 487-499, ISSN 1582-4934

DOI: 10.1111/jcmm.12993
PMID: 27680891

13 p, 680.7 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles