TY - JOUR
T1 - RANTES/CCL5 and risk for coronary events
T2 - results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.
AU - Herder, Christian
AU - Peeters, Wouter
AU - Illig, Thomas
AU - Baumert, Jens
AU - de Kleijn, Dominique P.V.
AU - Moll, Frans L.
AU - Poschen, Ulrike
AU - Klopp, Norman
AU - Müller-Nurasyid, Martina
AU - Roden, Michael
AU - Preuss, Michael
AU - CARDIoGRAM Consortium, Consortium
AU - Karakas, Mahir
AU - Meisinger, Christa
AU - Thorand, Barbara
AU - Pasterkamp, Gerard
AU - Koenig, Wolfgang
AU - Assimes, Themistocles L.
AU - Deloukas, Panos
AU - Erdmann, Jeanette
AU - Holm, Hilma
AU - Kathiresan, Sekar
AU - König, Inke R.
AU - McPherson, Ruth
AU - Reilly, Muredach P.
AU - Roberts, Robert
AU - Samani, Nilesh J.
AU - Schunkert, Heribert
AU - Stewart, Alexandre F.R.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=82855167348&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0025734
DO - 10.1371/journal.pone.0025734
M3 - Article
C2 - 22162987
AN - SCOPUS:82855167348
SN - 1932-6203
VL - 6
SP - e25734
JO - PLoS ONE
JF - PLoS ONE
IS - 12
ER -
