miR-505-3p controls chemokine receptor up-regulation in macrophages: role in familial hypercholesterolemia

Autor: Escate R, Mata P, Cepeda JM, Padró T, Badimon L
Rok vydání: 2018
Předmět:
chronic inflammation
chemokine receptor CCR4
chemokine receptor CCR3
TIRAP protein
CD40 antigen
low density lipoprotein cholesterol
gene targeting
toll like receptor 6
high density lipoprotein cholesterol
glucose
innate immunity
comparative study
cholic acid derivative
C reactive protein
inna
microRNA
familial hypercholesterolemia
beta 2 microglobulin
adult
chemokine receptor
inflammatory markers
cohort analysis
beta actin
microRNAs
unclassified drug
immunoglobulin enhancer binding protein
LDL cholesterol
MIRN505 microRNA
human
triacylglycerol
monocyte chemotactic protein 1
down regulation
transcription factor RUNX1
interleukin 10 receptor beta
cellular immunity
microrNA 505 3p
Article
glyceraldehyde 3 phosphate dehydrogenase
RANTES
ribosome protein
controlled study
human
hypoxanthine phosphoribosyltransferase
LDL cholesterol
age
inflammatory markers
innate immunity
microRNAs
chemokine receptor CXCR1
CD16 antigen
human cell
ADP ribosyl cyclase/cyclic ADP ribose hydrolase 1
cholesterol
CD14 antigen
age
genetic transfection
low density lipoprotein
adaptor protein
Zdroj: FASEB JOURNAL
r-FISABIO: Repositorio Institucional de Producción Científica
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname
r-FISABIO. Repositorio Institucional de Producción Científica
ISSN: 1530-6860
0892-6638
Popis: Familial hypercholesterolemia (FH) conveys a high risk of premature atherosclerosis as a result of lifelong exposure to high LDL cholesterol levels that are not fully reduced by standard-of-care lipid-lowering treatment. Inflammatory mediators have played a role in the progression of atherosclerotic lesions. Here, we investigated whether innate immunity cells in patients with FH have a specific proinflammatory phenotype that is distinct from that of cells in normal participants. To this end, miR-505-3p-a microRNA related to chronic inflammation-and its target genes were investigated in monocyte-derived macrophages (MACs) of patients with FH (FH-MACs) and non-FH controls (co-MACs). On the basis of the profiler PCR array analysis of agomiR-505-3p-transfected MACs, we identified the chemokine receptors, CCR3, CCR4, and CXCR1, as genes that are regulated by miR-505-3p via the transcription factor, RUNX1. miR-505-3p was significantly down-regulated, whereas CCR3, CCR4, CXCR, and RUNX1 were increased in FH-MAC compared with co-MAC, with the increase being more evident in the proinflammatory M1-like FH-MAC. Chemokine receptor levels were unrelated to LDL plasma levels at entry, but correlated with age in patients with FH, not in controls. In summary, we demonstrate for first time to our knowledge that MACs from FH-MACs have an inflammatory phenotype that is characterized by the up-regulation of CCR3, CCR4, and CXCR1 under the control of miR-505-3p. These results suggest a chronic inflammatory condition in FH innate immunity cells that is not reverted by standard lipid-lowering treatment.-Escate, R., Mata, P., Cepeda, J. M., Padr, T., Badimon, L. miR-505-3p controls chemokine receptor up-regulation in macrophages: role in familial hypercholesterolemia.
Databáze: OpenAIRE
Externí odkaz: