title: RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Wouter
authors.initials: W
authors.lastname: Peeters
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Jens
authors.initials: J
authors.lastname: Baumert
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Ulrike
authors.initials: U
authors.lastname: Poschen
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Martina
authors.initials: M
authors.lastname: Müller-Nurasyid
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Michael
authors.initials: M
authors.lastname: Preuss
authors.forename: Mahir
authors.initials: M
authors.lastname: Karakas
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Themistocles L
authors.initials: TL
authors.lastname: Assimes
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Ruth
authors.initials: R
authors.lastname: McPherson
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Robert
authors.initials: R
authors.lastname: Roberts
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Alexandre F R
authors.initials: AF
authors.lastname: Stewart
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D050197:Atherosclerosis / Q000097:blood*; D002114:Calcinosis / Q000097:blood; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood*; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D018946:Chemokine CCL5