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

Sekar Kathiresan; Muredach P. Reilly; Nilesh J. Samani; Heribert Schunkert; Jeanette Erdmann; Themistocles L. Assimes; Eric Boerwinkle; Alistair Hall; Christian Hengstenberg; Inke R. König; Reijo Laaksonen; Ruth McPherson; John R. Thompson; Unnur Thorsteinsdottir; Andreas Ziegler; Devin Absher; Li Chen; L. Adrienne Cupples; Eran Halperin; Mingyao Li; Kiran Musunuru; Michael Preuss; Arne Schillert; Gudmar Thorleifsson; Benjamin F. Voight; George A. Wells; Panos Deloukas; Hilma Holm; Robert Roberts; Alexandre F R Stewart; Stephen Fortmann; Alan Go; Mark Hlatky; Carlos Iribarren; Joshua Knowles; Richard Myers; Thomas Quertermous; Steven Sidney; Neil Risch; Hua Tang; Stefan Blankenberg; Tanja Zeller; Philipp Wild; Renate Schnabel; Christoph Sinning; Karl Lackner; Laurence Tiret; Viviane Nicaud; Francois Cambien; Christoph Bickel; Hans J. Rupprecht; Claire Perret; Carole Proust; Thomas Münzel; Maja Barbalic; Joshua Bis; Ida Yii Der Chen; Abbas Dehghan; Serkalem Demissie-Banjaw; Aaron Folsom; Nicole Glazer; Vilmundur Gudnason; Tamara Harris; Susan Heckbert; Daniel Levy; Thomas Lumley; Kristin Marciante; Alanna Morrison; Christopher J. O'Donnell; Bruce M. Psaty; Kenneth Rice; Jerome I. Rotter; David S. Siscovick; Nicholas Smith; Albert Smith; Kent D. Taylor; Cornelia van Duijn; Kelly Volcik; Jaqueline Whitteman; Vasan Ramachandran; Albert Hofman; Andre Uitterlinden; Solveig Gretarsdottir; Jeffrey R. Gulcher; Augustine Kong; Kari Stefansson; Gudmundur Thorgeirsson; Karl Andersen; Marcus Fischer; Anika Grosshennig; Wolfgang Lieb; Patrick Linsel-Nitschke; Klaus Stark; Stefan Schreiber; H. Erich Wichmann; Zouhair Aherrahrou; Petra Bruse; Angela Doering; Thomas Illig; Norman Klopp; Christina Loley; Anja Medack; Christina Meisinger; Thomas Meitinger; Janja Nahrstedt; Annette Peters; Arnika K. Wagner; Christina Willenborg; Bernhard O. Böhm; Harald Dobnig; Tanja B. Grammer; Michael M. Hoffmann; Marcus Kleber; Winfried März; Andreas Meinitzer; Bernhard R. Winkelmann; Stefan Pilz; Wilfried Renner; Hubert Scharnagl; Tatjana Stojakovic; Andreas Tomaschitz; Karl Winkler; Candace Guiducci; Noel Burtt; Stacey B. Gabriel; Roberto Elosua; Leena Peltonen; Veikko Salomaa; Stephen M. Schwartz; Olle Melander; David Altshuler; Sonny Dandona; Olga Jarinova; Liming Qu; Robert Wilensky; William Matthai; Hakon H. Hakonarson; Joe Devaney; Mary Susan Burnett; Augusto D. Pichard; Kenneth M. Kent; Lowell Satler; Joseph M. Lindsay; Ron Waksman; Christopher W. Knouff; Dawn M. Waterworth; Max C. Walker; Vincent Mooser; Stephen E. Epstein; Daniel J. Rader; Peter S. Braund; Christopher P. Nelson; Benjamin J. Wright; Anthony J. Balmforth; Stephen G. Ball

doi:10.1371/journal.pone.0025734

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

Sekar Kathiresan, Muredach P. Reilly, Nilesh J. Samani, Heribert Schunkert, Jeanette Erdmann, Themistocles L. Assimes, Eric Boerwinkle, Alistair Hall, Christian Hengstenberg, Inke R. König, Reijo Laaksonen, Ruth McPherson, John R. Thompson, Unnur Thorsteinsdottir, Andreas Ziegler, Devin Absher, Li Chen, L. Adrienne Cupples, Eran Halperin, Mingyao LiKiran Musunuru, Michael Preuss, Arne Schillert, Gudmar Thorleifsson, Benjamin F. Voight, George A. Wells, Panos Deloukas, Hilma Holm, Robert Roberts, Alexandre F R Stewart, Stephen Fortmann, Alan Go, Mark Hlatky, Carlos Iribarren, Joshua Knowles, Richard Myers, Thomas Quertermous, Steven Sidney, Neil Risch, Hua Tang, Stefan Blankenberg, Tanja Zeller, Philipp Wild, Renate Schnabel, Christoph Sinning, Karl Lackner, Laurence Tiret, Viviane Nicaud, Francois Cambien, Christoph Bickel, Hans J. Rupprecht, Claire Perret, Carole Proust, Thomas Münzel, Maja Barbalic, Joshua Bis, Ida Yii Der Chen, Abbas Dehghan, Serkalem Demissie-Banjaw, Aaron Folsom, Nicole Glazer, Vilmundur Gudnason, Tamara Harris, Susan Heckbert, Daniel Levy, Thomas Lumley, Kristin Marciante, Alanna Morrison, Christopher J. O'Donnell, Bruce M. Psaty, Kenneth Rice, Jerome I. Rotter, David S. Siscovick, Nicholas Smith, Albert Smith, Kent D. Taylor, Cornelia van Duijn, Kelly Volcik, Jaqueline Whitteman, Vasan Ramachandran, Albert Hofman, Andre Uitterlinden, Solveig Gretarsdottir, Jeffrey R. Gulcher, Augustine Kong, Kari Stefansson, Gudmundur Thorgeirsson, Karl Andersen, Marcus Fischer, Anika Grosshennig, Wolfgang Lieb, Patrick Linsel-Nitschke, Klaus Stark, Stefan Schreiber, H. Erich Wichmann, Zouhair Aherrahrou, Petra Bruse, Angela Doering, Thomas Illig, Norman Klopp, Christina Loley, Anja Medack, Christina Meisinger, Thomas Meitinger, Janja Nahrstedt, Annette Peters, Arnika K. Wagner, Christina Willenborg, Bernhard O. Böhm, Harald Dobnig, Tanja B. Grammer, Michael M. Hoffmann, Marcus Kleber, Winfried März, Andreas Meinitzer, Bernhard R. Winkelmann, Stefan Pilz, Wilfried Renner, Hubert Scharnagl, Tatjana Stojakovic, Andreas Tomaschitz, Karl Winkler, Candace Guiducci, Noel Burtt, Stacey B. Gabriel, Roberto Elosua, Leena Peltonen, Veikko Salomaa, Stephen M. Schwartz, Olle Melander, David Altshuler, Sonny Dandona, Olga Jarinova, Liming Qu, Robert Wilensky, William Matthai, Hakon H. Hakonarson, Joe Devaney, Mary Susan Burnett, Augusto D. Pichard, Kenneth M. Kent, Lowell Satler, Joseph M. Lindsay, Ron Waksman, Christopher W. Knouff, Dawn M. Waterworth, Max C. Walker, Vincent Mooser, Stephen E. Epstein, Daniel J. Rader, Peter S. Braund, Christopher P. Nelson, Benjamin J. Wright, Anthony J. Balmforth, Stephen G. Ball

Epidemiology & Community Health

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Article number	e25734
Journal	PloS one
Volume	6
Issue number	12
DOIs	https://doi.org/10.1371/journal.pone.0025734
State	Published - Dec 6 2011

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10.1371/journal.pone.0025734

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Kathiresan, S., Reilly, M. P., Samani, N. J., Schunkert, H., Erdmann, J., Assimes, T. L., Boerwinkle, E., Hall, A., Hengstenberg, C., König, I. R., Laaksonen, R., McPherson, R., Thompson, J. R., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, L. A., Halperin, E., ... Ball, S. G. (2011). RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies. PloS one, 6(12), Article e25734. https://doi.org/10.1371/journal.pone.0025734

Kathiresan, S, Reilly, MP, Samani, NJ, Schunkert, H, Erdmann, J, Assimes, TL, Boerwinkle, E, Hall, A, Hengstenberg, C, König, IR, Laaksonen, R, McPherson, R, Thompson, JR, Thorsteinsdottir, U, Ziegler, A, Absher, D, Chen, L, Cupples, LA, Halperin, E, Li, M, Musunuru, K, Preuss, M, Schillert, A, Thorleifsson, G, Voight, BF, Wells, GA, Deloukas, P, Holm, H, Roberts, R, Stewart, AFR, Fortmann, S, Go, A, Hlatky, M, Iribarren, C, Knowles, J, Myers, R, Quertermous, T, Sidney, S, Risch, N, Tang, H, Blankenberg, S, Zeller, T, Wild, P, 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, Chen, IYD, 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, Kong, A, Stefansson, K, Thorgeirsson, G, Andersen, K, Fischer, M, Grosshennig, A, Lieb, W, Linsel-Nitschke, P, Stark, K, Schreiber, S, Wichmann, HE, Aherrahrou, Z, Bruse, P, Doering, A, Illig, T, Klopp, N, Loley, C, Medack, A, Meisinger, C, Meitinger, T, Nahrstedt, J, Peters, A, Wagner, AK, Willenborg, C, Böhm, BO, Dobnig, H, Grammer, TB, Hoffmann, MM, Kleber, M, März, W, Meinitzer, A, Winkelmann, BR, Pilz, S, Renner, W, Scharnagl, H, Stojakovic, T, Tomaschitz, A, Winkler, K, Guiducci, C, Burtt, N, Gabriel, SB, Elosua, R, Peltonen, L, Salomaa, V, Schwartz, SM, Melander, O, Altshuler, D, Dandona, S, Jarinova, O, 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, Braund, PS, Nelson, CP, Wright, BJ, Balmforth, AJ & Ball, SG 2011, 'RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies', PloS one, vol. 6, no. 12, e25734. https://doi.org/10.1371/journal.pone.0025734

@article{7e495d56a160435494267635bdb13085,

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. 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.",

author = "Sekar Kathiresan and Reilly, {Muredach P.} and Samani, {Nilesh J.} and Heribert Schunkert and Jeanette Erdmann and Assimes, {Themistocles L.} and Eric Boerwinkle and Alistair Hall and Christian Hengstenberg and K{\"o}nig, {Inke R.} and Reijo Laaksonen and Ruth McPherson and Thompson, {John R.} and Unnur Thorsteinsdottir and Andreas Ziegler and Devin Absher and Li Chen and Cupples, {L. Adrienne} and Eran Halperin and Mingyao Li and Kiran Musunuru and Michael Preuss and Arne Schillert and Gudmar Thorleifsson and Voight, {Benjamin F.} and Wells, {George A.} and Panos Deloukas and Hilma Holm and Robert Roberts and Stewart, {Alexandre F R} and Stephen Fortmann and Alan Go and Mark Hlatky and Carlos Iribarren and Joshua Knowles and Richard Myers and Thomas Quertermous and Steven Sidney and Neil Risch and Hua Tang and Stefan Blankenberg and Tanja Zeller and Philipp Wild and Renate Schnabel and Christoph Sinning and Karl Lackner and Laurence Tiret and Viviane Nicaud and Francois Cambien and Christoph Bickel and Rupprecht, {Hans J.} and Claire Perret and Carole Proust and Thomas M{\"u}nzel and Maja Barbalic and Joshua Bis and Chen, {Ida Yii Der} and Abbas Dehghan and Serkalem Demissie-Banjaw and Aaron Folsom and Nicole Glazer and Vilmundur Gudnason and Tamara Harris and Susan Heckbert and Daniel Levy and Thomas Lumley and Kristin Marciante and Alanna Morrison and O'Donnell, {Christopher J.} and Psaty, {Bruce M.} and Kenneth Rice and Rotter, {Jerome I.} and Siscovick, {David S.} and Nicholas Smith and Albert Smith and Taylor, {Kent D.} and {van Duijn}, Cornelia and Kelly Volcik and Jaqueline Whitteman and Vasan Ramachandran and Albert Hofman and Andre Uitterlinden and Solveig Gretarsdottir and Gulcher, {Jeffrey R.} and Augustine Kong and Kari Stefansson and Gudmundur Thorgeirsson and Karl Andersen and Marcus Fischer and Anika Grosshennig and Wolfgang Lieb and Patrick Linsel-Nitschke and Klaus Stark and Stefan Schreiber and Wichmann, {H. Erich} and Zouhair Aherrahrou and Petra Bruse and Angela Doering and Thomas Illig and Norman Klopp and Christina Loley and Anja Medack and Christina Meisinger and Thomas Meitinger and Janja Nahrstedt and Annette Peters and Wagner, {Arnika K.} and Christina Willenborg and B{\"o}hm, {Bernhard O.} and Harald Dobnig and Grammer, {Tanja B.} and Hoffmann, {Michael M.} and Marcus Kleber and Winfried M{\"a}rz and Andreas Meinitzer and Winkelmann, {Bernhard R.} and Stefan Pilz and Wilfried Renner and Hubert Scharnagl and Tatjana Stojakovic and Andreas Tomaschitz and Karl Winkler and Candace Guiducci and Noel Burtt and Gabriel, {Stacey B.} and Roberto Elosua and Leena Peltonen and Veikko Salomaa and Schwartz, {Stephen M.} and Olle Melander and David Altshuler and Sonny Dandona and Olga Jarinova and Liming Qu and Robert Wilensky and William Matthai and Hakonarson, {Hakon H.} and Joe Devaney and Burnett, {Mary Susan} and Pichard, {Augusto D.} and Kent, {Kenneth M.} and Lowell Satler and Lindsay, {Joseph M.} and Ron Waksman and Knouff, {Christopher W.} and Waterworth, {Dawn M.} and Walker, {Max C.} and Vincent Mooser and Epstein, {Stephen E.} and Rader, {Daniel J.} and Braund, {Peter S.} and Nelson, {Christopher P.} and Wright, {Benjamin J.} and Balmforth, {Anthony J.} and Ball, {Stephen G.}",

year = "2011",

month = dec,

day = "6",

doi = "10.1371/journal.pone.0025734",

language = "English (US)",

volume = "6",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "12",

}

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 - Kathiresan, Sekar

AU - Reilly, Muredach P.

AU - Samani, Nilesh J.

AU - Schunkert, Heribert

AU - Erdmann, Jeanette

AU - Assimes, Themistocles L.

AU - Boerwinkle, Eric

AU - Hall, Alistair

AU - Hengstenberg, Christian

AU - König, Inke R.

AU - Laaksonen, Reijo

AU - McPherson, Ruth

AU - Thompson, John R.

AU - Thorsteinsdottir, Unnur

AU - Ziegler, Andreas

AU - Absher, Devin

AU - Chen, Li

AU - Cupples, L. Adrienne

AU - Halperin, Eran

AU - Li, Mingyao

AU - Musunuru, Kiran

AU - Preuss, Michael

AU - Schillert, Arne

AU - Thorleifsson, Gudmar

AU - Voight, Benjamin F.

AU - Wells, George A.

AU - Deloukas, Panos

AU - Holm, Hilma

AU - Roberts, Robert

AU - Stewart, Alexandre F R

AU - Fortmann, Stephen

AU - Go, Alan

AU - Hlatky, Mark

AU - Iribarren, Carlos

AU - Knowles, Joshua

AU - Myers, Richard

AU - Quertermous, Thomas

AU - Sidney, Steven

AU - Risch, Neil

AU - Tang, Hua

AU - Blankenberg, Stefan

AU - Zeller, Tanja

AU - Wild, Philipp

AU - Schnabel, Renate

AU - Sinning, Christoph

AU - Lackner, Karl

AU - Tiret, Laurence

AU - Nicaud, Viviane

AU - Cambien, Francois

AU - Bickel, Christoph

AU - Rupprecht, Hans J.

AU - Perret, Claire

AU - Proust, Carole

AU - Münzel, Thomas

AU - Barbalic, Maja

AU - Bis, Joshua

AU - Chen, Ida Yii Der

AU - Dehghan, Abbas

AU - Demissie-Banjaw, Serkalem

AU - Folsom, Aaron

AU - Glazer, Nicole

AU - Gudnason, Vilmundur

AU - Harris, Tamara

AU - Heckbert, Susan

AU - Levy, Daniel

AU - Lumley, Thomas

AU - Marciante, Kristin

AU - Morrison, Alanna

AU - O'Donnell, Christopher J.

AU - Psaty, Bruce M.

AU - Rice, Kenneth

AU - Rotter, Jerome I.

AU - Siscovick, David S.

AU - Smith, Nicholas

AU - Smith, Albert

AU - Taylor, Kent D.

AU - van Duijn, Cornelia

AU - Volcik, Kelly

AU - Whitteman, Jaqueline

AU - Ramachandran, Vasan

AU - Hofman, Albert

AU - Uitterlinden, Andre

AU - Gretarsdottir, Solveig

AU - Gulcher, Jeffrey R.

AU - Kong, Augustine

AU - Stefansson, Kari

AU - Thorgeirsson, Gudmundur

AU - Andersen, Karl

AU - Fischer, Marcus

AU - Grosshennig, Anika

AU - Lieb, Wolfgang

AU - Linsel-Nitschke, Patrick

AU - Stark, Klaus

AU - Schreiber, Stefan

AU - Wichmann, H. Erich

AU - Aherrahrou, Zouhair

AU - Bruse, Petra

AU - Doering, Angela

AU - Illig, Thomas

AU - Klopp, Norman

AU - Loley, Christina

AU - Medack, Anja

AU - Meisinger, Christina

AU - Meitinger, Thomas

AU - Nahrstedt, Janja

AU - Peters, Annette

AU - Wagner, Arnika K.

AU - Willenborg, Christina

AU - Böhm, Bernhard O.

AU - Dobnig, Harald

AU - Grammer, Tanja B.

AU - Hoffmann, Michael M.

AU - Kleber, Marcus

AU - März, Winfried

AU - Meinitzer, Andreas

AU - Winkelmann, Bernhard R.

AU - Pilz, Stefan

AU - Renner, Wilfried

AU - Scharnagl, Hubert

AU - Stojakovic, Tatjana

AU - Tomaschitz, Andreas

AU - Winkler, Karl

AU - Guiducci, Candace

AU - Burtt, Noel

AU - Gabriel, Stacey B.

AU - Elosua, Roberto

AU - Peltonen, Leena

AU - Salomaa, Veikko

AU - Schwartz, Stephen M.

AU - Melander, Olle

AU - Altshuler, David

AU - Dandona, Sonny

AU - Jarinova, Olga

AU - Qu, Liming

AU - Wilensky, Robert

AU - Matthai, William

AU - Hakonarson, Hakon H.

AU - Devaney, Joe

AU - Burnett, Mary Susan

AU - Pichard, Augusto D.

AU - Kent, Kenneth M.

AU - Satler, Lowell

AU - Lindsay, Joseph M.

AU - Waksman, Ron

AU - Knouff, Christopher W.

AU - Waterworth, Dawn M.

AU - Walker, Max C.

AU - Mooser, Vincent

AU - Epstein, Stephen E.

AU - Rader, Daniel J.

AU - Braund, Peter S.

AU - Nelson, Christopher P.

AU - Wright, Benjamin J.

AU - Balmforth, Anthony J.

AU - Ball, Stephen G.

PY - 2011/12/6

Y1 - 2011/12/6

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=84880505530&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0025734

DO - 10.1371/journal.pone.0025734

M3 - Article

C2 - 22162987

AN - SCOPUS:84880505530

SN - 1932-6203

VL - 6

JO - PloS one

JF - PloS one

IS - 12

M1 - e25734

ER -

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

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