Chemokines in children with heterozygous familiar hypercholesterolemia: selective upregulation of RANTES.
OBJECTIVE
Increasing data support the involvement of chemokines in atherogenesis. However, although several studies have shown increased chemokine levels in adult patients, the literature is virtually devoid of data on chemokines in children with hypercholesterolemia.


RESULTS
We examined the gene expression of chemokines in peripheral blood mononuclear cells (PBMCs) from clinically healthy children with and without heterozygous familial hypercholesterolemia (FH). Our main findings were: (1) compared with healthy controls, PBMCs from FH children showed significantly higher mRNA levels of RANTES, but not of the other examined chemokines; (2) an opposite pattern was seen in adult FH subjects, with markedly enhanced expression of macrophage inflammatory peptide-1alpha, but not of RANTES; (3) this increased gene expression of RANTES in PBMCs from FH children seemed to reflect enhanced RANTES expression in monocytes but not in T cells; (4) FH children also had raised serum levels of neopterin, additionally suggesting monocyte/macrophage activation in these children; and (5) PBMCs from both FH children and controls showed enhanced release of interleukin 8 on RANTES stimulation in vitro.


CONCLUSIONS
Our findings support a role of inflammation also in the early stages of atherogenesis possibly involving monocyte-derived RANTES as an important mediator.
Holven
Kirsten B
KB
Research Institute for Internal Medicine, Lipid Clinic, Rikshospitalet, University of Oslo, Norway. kirsten.holven@medisin.uio.no
Damås
Jan K
JK
Yndestad
Arne
A
Waehre
Torgun
T
Ueland
Thor
T
Halvorsen
Bente
B
Heggelund
Lars
L
Sandberg
Wiggo J
WJ
Semb
Anne G
AG
Frøland
Stig S
SS
Ose
Leiv
L
Nenseter
Marit S
MS
Aukrust
Pål
P
D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000494:pharmacology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019798:Neopterin / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D018834:Chaperonin 60; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016209:Interleukin-8; D008077:Lipoproteins, LDL; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D019798:Neopterin