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.