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


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RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.
Plos One
Herder C., Peeters W., Illig T., Baumert J., de Kleijn D.P., Moll F.L., Poschen U., Klopp N., Müller-Nurasyid M., Roden M., Preuss M., Karakas M., Karakas M., Meisinger C., Thorand B., Pasterkamp G., Koenig W., Assimes T.L., Deloukas P., Erdmann J., Holm H., Kathiresan S., König I.R., McPherson R., Reilly M.P., Roberts R., Samani N.J., Schunkert H., Stewart A.F.
Working group(s)
CARDIoGRAM Consortium
Kathiresan S., Reilly MP., Samani NJ., Schunkert H., Erdmann J., Assimes TL., Boerwinkle E., Erdmann J., Hall A., Hengstenberg C., Kathiresan S., König IR., Laaksonen R., McPherson R., Reilly MP., Samani NJ., Schunkert H., Thompson JR., Thorsteinsdottir U., Ziegler A., König IR., Thompson JR., Absher D., Chen L., Cupples LA., Halperin E., Li M., Musunuru K., Preuss M., Schillert A., Thorleifsson G., Voight BF., Wells GA., Assimes TL., Deloukas P., Erdmann J., Holm H., Kathiresan S., König IR., McPherson R., Reilly MP., Roberts R., Samani NJ., Schunkert H., Stewart AF., Absher D., Assimes TL., Fortmann S., Go A., Hlatky M., Iribarren C., Knowles J., Myers R., Quertermous T., Sidney S., Risch N., Tang H., Blankenberg S., Zeller T., Schillert A., Wild P., Ziegler A., Schnabel R., Sinning C., Lackner K., Tiret L., Nicaud V., Cambien F., Bickel C., Rupprecht HJ., Perret C., Proust C., Münzel T., Barbalic M., Bis J., Boerwinkle E., Chen IY., Cupples LA., Dehghan A., Demissie-Banjaw S., Folsom A., Glazer N., Gudnason V., Harris T., Heckbert S., Levy D., Lumley T., Marciante K., Morrison A., O'Donnell CJ., Psaty BM., Rice K., Rotter JI., Siscovick DS., Smith N., Smith A., Taylor KD., van Duijn C., Volcik K., Whitteman J., Ramachandran V., Hofman A., Uitterlinden A., Gretarsdottir S., Gulcher JR., Holm H., Kong A., Stefansson K., Thorgeirsson G., Andersen K., Thorleifsson G., Thorsteinsdottir U., Erdmann J., Fischer M., Grosshennig A., Hengstenberg C., König IR., Lieb W., Linsel-Nitschke P., Preuss M., Stark K., Schreiber S., Wichmann HE., Ziegler A., Schunkert H., Aherrahrou Z., Bruse P., Doering A., Erdmann J., Hengstenberg C., Illig T., Klopp N., König IR., Linsel-Nitschke P., Loley C., Medack A., Meisinger C., Meitinger T., Nahrstedt J., Peters A., Preuss M., Stark K., Wagner AK., Wichmann HE., Willenborg C., Ziegler A., Schunkert H., Böhm BO., Dobnig H., Grammer TB., Halperin E., Hoffmann MM., Kleber M., Laaksonen R., März W., Meinitzer A., Winkelmann BR., Pilz S., Renner W., Scharnagl H., Stojakovic T., Tomaschitz A., Winkler K., Voight BF., Musunuru K., Guiducci C., Burtt N., Gabriel SB., Siscovick DS., O'Donnell CJ., Elosua R., Peltonen L., Salomaa V., Schwartz SM., Melander O., Altshuler D., Kathiresan S., Stewart AF., Chen L., Dandona S., Wells GA., Jarinova O., McPherson R., Roberts R., Reilly MP., Li M., Qu L., Wilensky R., Matthai W., Hakonarson HH., Devaney J., Burnett MS., Pichard AD., Kent KM., Satler L., Lindsay JM., Waksman R., Knouff CW., Waterworth DM., Walker MC., Mooser V., Epstein SE., Rader DJ., Samani NJ., Thompson JR., Braund PS., Nelson CP., Wright BJ., Balmforth AJ., Ball SG., Hall AS.
1932-6203 (Electronic)
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Issued date
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
METHODS AND FINDINGS: 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.
Adult, Aged, Animals, Atherosclerosis/blood, Calcinosis/blood, Case-Control Studies, Chemokine CCL5/blood, Cohort Studies, Coronary Disease/blood, Coronary Disease/diagnosis, Female, Follow-Up Studies, Germany, Humans, Macrophages/cytology, Male, Mice, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk
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Open Access
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22/03/2012 9:44
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20/08/2019 14:43
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