Tendon xanthomas in familial hypercholesterolemia are associated with a differential inflammatory response of macrophages to oxidized LDL.
Tendon xanthomas (TX) are pathognomonic lipid deposits commonly found in familial hypercholesterolemia (FH) patients. The aim of this study was to determine whether macrophages from FH patients with TX (TX+) have higher predisposition to foam cells formation after oxidized LDL (oxLDL) overload than those from FH patients without TX (TX-), and if their differential gene expression profile could explain these different phenotypes. Total RNA pools from macrophages from FH patients TX+ and TX- were analyzed using Affymetrix oligonucleotide arrays to evaluate the gene expression profile in presence and absence of oxLDL. Also, the intracellular lipid content was measured by fluorescence flow cytometry. Results of these studies suggest that macrophages from FH subjects TX+ compared to those TX- have a differential response to oxLDL, since they show higher intracellular cholesterol ester accumulation and a differential gene expression profile. The gene array data were validated by relative quantitative real-time RT-PCR and quantitative ELISA in culture media and plasma samples. FH subjects TX+ showed increased plasma tryptase, TNF-alpha, IL-8 and IL-6 concentrations. We propose that TX formation are associated with higher intracellular lipid content, and higher inflammatory response of macrophages in response to oxLDL.
Artieda
Marta
M
Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud, Isabel la Católica 1-3, Zaragoza 50009, Spain. martieda@salud.aragon.es
Cenarro
Ana
A
Junquera
Corina
C
Lasierra
Pilar
P
Martínez-Lorenzo
María José
MJ
Pocoví
Miguel
M
Civeira
Fernando
F
D002788:Cholesterol Esters / Q000032:analysis; D008078:Cholesterol, LDL / Q000494:pharmacology; D005487:Foam Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D013710:Tendons; D014973:Xanthomatosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein