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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_83631D215DFA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.
Journal
Plos One
Author(s)
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
Contributor(s)
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.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2011
Volume
6
Number
12
Pages
e25734
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
22/03/2012 9:44
Last modification date
20/08/2019 14:43
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