Abstract
Summary
Patients with familial hypercholesterolemia (FH) have an increased risk of premature atherosclerosis and coronary artery disease (CAD). Recently, inflammation has been suggested to play a major role in the development of atherosclerosis, and indeed children with FH have previously been suggested to have increased levels of selective inflammation markers. The aim of this study was to increase the knowledge about inflammation in the early steps of atherosclerosis.
Sixty-two FH children (aged 7-20 years) and twenty-two sex- and age-matched control children were included. Quantification of the circulating proteins soluble (s)E-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), adiponectin and leptin was performed in serum samples from each subject. Furthermore, gene expression levels of tumor necrosis factor á (TNFá), ICAM-1 and leptin receptor in peripheral blood mononuclear cells (PBMCs) were determined by quantitative reverse transcription polymerase chain reaction (Q-RT-PCR).
The main results showed: i) FH children have increased TNFá gene expression levels and a tendency to increased sE-selectin levels compared to control children; ii) FH boys have enhanced sE-selectin and sVCAM-1 levels compared to FH girls; iii) FH boys above 15 years have increased levels of sE-selectin compared to age-matched FH girls; iv) FH boys below 15 years have enhanced levels of sVCAM-1 compared to FH girls in the same age group; v) FH girls have enhanced leptin levels compared to FH boys; vi) there was a tendency to enhanced leptin levels, whereas adiponectin levels were decreased in FH children above 15 years compared to FH children below 15 years.
In conclusion, our results may support the notion of increased inflammation in FH children. Furthermore, the results may also indicate that the gender difference in the levels of early atherosclerotic markers may be established already in childhood and may thus partly explain the gender difference in the risk of CVD.