RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.

The chemokine RANTES (regulated on activation, normal T-cell
expressed and secreted)/CCL5 is involved in the pathogenesis of
cardiovascular disease in mice, whereas less is known in humans. We
hypothesised that its relevance for atherosclerosis should be
reflected by associations between CCL5 gene variants, RANTES serum
concentrations and protein levels in atherosclerotic plaques and
risk for coronary events. We conducted a case-cohort study within
the population-based MONICA/KORA Augsburg studies. Baseline RANTES
serum levels were measured in 363 individuals with incident
coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8
years). Cox proportional hazard models adjusting for age, sex, body
mass index, metabolic factors and lifestyle factors revealed no
significant association between RANTES and incident coronary events
(HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42]
and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide
polymorphisms and no common haplotype showed significant
associations with coronary events. Also in the CARDIoGRAM study
(>22,000 cases, >60,000 controls), none of these CCL5 SNPs
was significantly associated with coronary artery disease. In the
prospective Athero-Express biobank study, RANTES plaque levels were
measured in 606 atherosclerotic lesions from patients who underwent
carotid endarterectomy. RANTES content in atherosclerotic plaques
was positively associated with macrophage infiltration and
inversely associated with plaque calcification. However, there was
no significant association between RANTES content in plaques and
risk for coronary events (mean follow-up 2.8±0.8 years). High
RANTES plaque levels were associated with an unstable plaque
phenotype. However, the absence of associations between (i) RANTES
serum levels, (ii) CCL5 genotypes and (iii) RANTES content in
carotid plaques and either coronary artery disease or incident
coronary events in our cohorts suggests that RANTES may not be a
novel coronary risk biomarker. However, the potential relevance of
RANTES levels in platelet-poor plasma needs to be investigated in
further studies.