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  • Title: Poloxamer 407 increases soluble adhesion molecules, ICAM-1, VCAM-1 and E-selectin, in C57BL/6 mice.
    Author: Johnston TP.
    Journal: J Pharm Pharmacol; 2009 Dec; 61(12):1681-8. PubMed ID: 19958592.
    Abstract:
    OBJECTIVES: Soluble shedded forms of cell adhesion molecules (sCAMs) found in plasma are regarded as surrogate markers for the cellular expression of CAMs. The presence of oxidised low-density lipoprotein (ox-LDL) cholesterol and fatty acids in the plasma, hypertriglyceridaemia and reduced plasma concentrations of high-density lipoprotein cholesterol (HDL-C) are all thought to stimulate an increase in the cellular expression of CAMs such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Our objectives were to determine how plasma levels of the soluble CAMs were modulated in a mouse model of dyslipidaemia induced chemically with poloxamer 407, and how these changes might be related to changes in the plasma concentrations of total cholesterol, HDL-C, non-HDL-C and triglycerides. METHODS: C57BL/6 mice were given a single intraperitoneal dose of poloxamer 407 (0.5 ;g/kg) and plasma concentrations of lipid fractions and sCAMs were measured at predetermined time points thereafter. KEY FINDINGS: The plasma concentrations of each sCAM were significantly increased in our mouse model of atherogenic dyslipidaemia compared with control mice administered saline, although the temporal relationship between the plasma sCAM concentration-time profiles and the plasma lipid concentration-time profiles were not coincident. CONCLUSIONS: The atherogenic profile in our mouse model was associated with increases in the plasma concentrations of sICAM-1, sVCAM-1 and sE-selectin. These changes precede the formation of atherosclerotic lesions shown in previous work. This suggests the use of these sCAMs as biomarkers of future atheroma formation in this particular animal model.
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