Low level of inflammatory marker in hyperhomocysteinemic patients on statin therapy.
Inflammatory processes including increased activation of chemokines play an important role in atherogenesis. Patients with hyperhomocysteinemia have increased risk for cardiovascular events that potentially involve enhanced inflammation. Statins may have anti-inflammatory actions at least partly independent on their lipid-lowering effects. In the present study we examined the association between statins and chemokine levels in patients with hyperhomocysteinemia. Our major findings were (i) patients with hyperhomocysteinemia on statin treatment (n = 14) have significantly lower plasma levels of the CXC chemokine epithelial neutrophil activating peptide (ENA)-78 compared to hyperhomocysteinemic patients not on statin treatment (n = 8). In fact, levels of ENA-78 in statin-treated patients did not differ from those of healthy controls (n = 17); (ii) plasma levels of ENA-78 and growth-related oncogene (GRO)α correlated with levels of LDL-cholesterol and homocysteine; (iii) in contrast, plasma levels of the CC chemokine monocyte chemoattractant peptide (MCP)-1 were similar between statin-users, non-statin users and controls, and did not correlate with levels of LDL-cholesterol or homocysteine; and (iv) in vitro studies showed that simvastatin significantly reduced release of ENA-78, GROα and MCP-1 from peripheral blood mononuclear cells in healthy controls (n = 7) in a concentration-dependent manner, without affecting release of RANTES. Our data may suggest that ENA-78 and GROα may be involved in the inflammatory arm of atherogenesis in patients with elevated risk of cardiovascular disease, with potential down-regulatory effect of statins.
The Lipid Clinic.
Marit S
MS
Nenseter
Pål
P
Aukrust
Leiv
L
Ose
Kirsten B
KB
Holven
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood* / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000188:drug therapy; D018836:Inflammation Mediators / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use; D055815:Young Adult
D015415:Biomarkers; D018925:Chemokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin