Cystatin C levels in plasma and peripheral blood mononuclear cells among hyperhomocysteinaemic 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 hyperhomocysteinaemia 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 hyperhomocysteinaemic individuals (n 37, female seven and male thirty, aged 20-70 years) before and after B-vitamin supplementation for 3 months in a randomised, placebo-controlled double-blind trial. In a cross-sectional study, seventeen of the hyperhomocysteinaemic subjects were age- and sex-matched to healthy controls (n 17). Our main findings were: (i) as compared with controls, hyperhomocysteinaemic 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 hyperhomocysteinaemic 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 hyperhomocysteinaemic individuals, potentially related to low-grade systemic inflammation in hyperhomocysteinaemic subjects, and that B-vitamins may modulate cystatin C levels in these individuals.
Tobin
Kari Anne R
KA
Lipid Clinic, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Holven
Kirsten B
KB
Retterstøl
Kjetil
K
Strøm
Ellen
E
Ose
Leiv
L
Aukrust
Pål
P
Nenseter
Marit S
MS
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000097:blood* / Q000235:genetics; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012333:RNA, Messenger / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D014805:Vitamin B 12 / Q000008:administration & dosage; D025101:Vitamin B 6 / Q000008:administration & dosage; D014803:Vitamin B Complex / Q000008:administration & dosage*
D055316:Cystatin C; D010919:Placebos; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D014803:Vitamin B Complex; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12