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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:200.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Chemokines in Children With Heterozygous Familiar Hypercholesterolemia

Selective Upregulation of RANTES

Kirsten B. Holven; Jan K. Damås; Arne Yndestad; Torgun Wæhre; Thor Ueland; Bente Halvorsen; Lars Heggelund; Wiggo J. Sandberg; Anne G. Semb; Stig S. Frøland; Leiv Ose; Marit S. Nenseter; Pål Aukrust

From the Research Institute for Internal Medicine (K.B.H., J.K.D., A.Y., T.W., T.U., B.H., L.H., W.J.S., S.S.F., M.S.N., P.A.), Lipid Clinic (K.B.H., A.G.S., L.O., M.S.N.), Department of Cardiology (J.K.D., T.W.), Section of Endocrinology (T.U.), and Section of Clinical Immunology and Infectious Diseases (L.H., S.S.F., P.A.), Rikshospitalet, University of Oslo, Norway.

Correspondence to Kirsten B. Holven, Research Institute for Internal Medicine/Lipid Clinic, Rikshospitalet, N-0027 Oslo, Norway. E-mail kirsten.holven{at}medisin.uio.no

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.

Methods and 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-1, 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.

Herein we show that children with heterozygous familial hypercholesterolemia are characterized by enhanced expression of RANTES but not of the other measured chemokines in peripheral blood mononuclear cells. Our findings support a role for inflammation also in the early stages of atherogenesis possibly involving RANTES as an important mediator.

Key Words: atherosclerosis • hypercholesterolemia • inflammation • RANTES • leukocytes

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