Cystatin C levels in plasma and peripheral blood mononuclear cells among hyperhomocysteinemic subjects: effect of treatment with B-vitamins

Homocysteine has been related to increased risk of CVD. Matrix degradation and inflammation may be involved in this link between hyperhomocysteinemia and CVD. Recent studies suggest that cystatin C can modulate matrix degradation and inflammation. The present study measured cystatin C at protein (plasma) and mRNA levels (peripheral blood mononuclear cells (PBMC)) in hyperhomocysteinemic individuals (n 37, female seven and male thirty, aged 20-70 years) before and after B-vitamin supplementation for 3 months in a randomized, placebo-controlled double-blind trial. In a cross-sectional study, seventeen of the hyperhomocysteinemic subjects were age- and sex-matched to healthy controls (n 17). Our main findings were: (i) as compared with controls, hyperhomocysteinemic subjects tended to have higher plasma concentrations of cystatin C and lower mRNA levels of cystatin C in PBMC; (ii) compared with placebo, treatment of hyperhomocysteinemic individuals with B-vitamins significantly increased plasma levels of cystatin C and mRNA levels of cystatin C in PBMC; (iii) while plasma levels of cystatin C were positively correlated with plasma levels of TNF receptor-1, mRNA levels of cystatin C in PBMC were inversely correlated with this TNF parameter. Taken together, our findings suggest that disturbed cystatin C levels may be a characteristic of hyperhomocysteinemic individuals, potentially related to low-grade systemic inflammation in hyperhomocysteinemic subjects, and that B-vitamins may modulate cystatin C levels in these individuals. [PUBLICATION ABSTRACT]