Serum cystatin C and chitotriosidase in acute P-407 induced dyslipidemia: Can they serve as potential early biomarkers for atherosclerosis?

In an attempt to better understand potential biomarkers for, and the role of macrophages in, the development of atherosclerosis, the toxicologic, and any therapeutic pharmacologic effects of carboxymethylated β-glucan, gadolinium chloride, and poloxamer 407 were studied in mice for their capacity to perturb serum lipids, cystatin C, and chitotriosidase-1. Gadolinium and carboxymethylated β-glucan dosed separately to control mice had no effect on serum lipids, whereas carboxymethylated β-glucan, but not gadolinium, exerted a significant (p < 0.01) and unexpected hypolipidemic effect in poloxamer 407-induced hyperlipidemic mice. An acute hyperlipidemic state (∼4 days), induced with poloxamer 407 administration alone, resulted in a significant (p < 0.01) time-dependent decrease and increase in serum cystatin C and chitotriosidase, respectively. Carboxymethylated β-glucan administration to hyperlipidemic mice significantly (p < 0.05) increased the serum concentration of cystatin C, but significantly (p < 0.01) decreased chitotriosidase activity, when each was compared to mice treated with poloxamer 407 only. Gadolinium administration caused a significant decrease in serum chitotriosidase activity in both controls (p < 0.01) and poloxamer 407-induced hyperlipidemic (p < 0.001) mice, but had no effect on the concentration of cystatin C in either controls or poloxamer 407-induced hyperlipidemic mice. Gadolinium administration resulted in both morphological and functional changes to liver macrophages, which included incorporation of excess lipids, especially when simultaneously administered with poloxamer 407. It is suggested that serum cystatin C and chitotriosidase may represent potential early biomarkers for eventual atherosclerosis in the poloxamer 407-induced mouse model of atherogenesis, and that two compounds known to either increase (carboxymethylated β-glucan) or decrease (gadolinium chloride) the number of macrophages in vivo were able to modulate serum chitotriosidase activity, This, in turn, would appear to support the premise that serum chitotriosidase activity may be a more sensitive indicator of macrophage involvement than cystatin C in the context of future atherosclerosis.