HMGB1 Is Associated with Atherosclerotic Plaque Composition and Burden in Patients with Stable Coronary Artery Disease

被引:55
作者
Andrassy, Martin [1 ]
Volz, H. Christian [1 ]
Schuessler, Alena [1 ]
Gitsioudis, Gitsios [1 ]
Hofmann, Nina [1 ]
Laohachewin, Danai [1 ]
Wienbrandt, Alexandra R. [1 ]
Kaya, Ziya [1 ]
Bierhaus, Angelika [2 ]
Giannitsis, Evangelos [1 ]
Katus, Hugo A. [1 ]
Korosoglou, Grigorios [1 ]
机构
[1] Heidelberg Univ, Dept Cardiol, D-6900 Heidelberg, Germany
[2] Heidelberg Univ, Dept Internal Med & Clin Chem 3, Heidelberg, Germany
来源
PLOS ONE | 2012年 / 7卷 / 12期
关键词
C-REACTIVE PROTEIN; MOBILITY GROUP BOX-1; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; SMOOTH-MUSCLE-CELLS; HEART-DISEASE; HIGH-MOBILITY-GROUP-BOX-1; PROTEIN; INFLAMMATION; LESIONS; RISK; MECHANISMS;
D O I
10.1371/journal.pone.0052081
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Objectives: The role of inflammation in atherosclerosis is widely appreciated. High mobility group box 1 (HMGB1), an injury-associated molecular pattern molecule acting as a mediator of inflammation, has recently been implicated in the development of atherosclerosis. In this study, we sought to investigate the association of plasma HMGB1 with coronary plaque composition in patients with suspected or known coronary artery disease (CAD). Design: HMGB1, high sensitive troponin T (hsTnT) and high sensitive C-reactive protein (hsCRP) were determined in 152 consecutive patients with suspected or known stable CAD who underwent clinically indicated 256-slice coronary computed tomography angiography (CCTA). Using CCTA, we assessed 1) coronary calcification, 2) non-calcified plaque burden and 3) the presence of vascular remodeling in areas of non-calcified plaques. Results: Using univariate analysis, hsCRP, hsTnT and HMGB1 as well as age, and atherogenic risk factors were associated with non-calcified plaque burden (r = 0.21, p = 0.009; r = 0.48, p<0.001 and r = 0.34, p<0.001, respectively). By multivariate analysis, hsTnT and HMGB1 remained independent predictors of the non-calcified plaque burden (r = 0.48, p<0.01 and r = 0.34, p<0.001, respectively), whereas a non-significant trend was noticed for hs-CRP (r = 0.21, p = 0.07). By combining hsTnT and HMGB1, a high positive predictive value for the presence of non-calcified and remodeled plaque (96% and 77%, respectively) was noted in patients within the upper tertiles for both biomarkers, which surpassed the positive predictive value of each marker separately. Conclusions: In addition to hs-TnT, a well-established cardiovascular risk marker, HMGB1 is independently associated with non-calcified plaque burden in patients with stable CAD, while the predictive value of hs-CRP is lower. Complementary value was observed for hs-TnT and HMGB1 for the prediction of complex coronary plaque.
引用
收藏
页数:9
相关论文
共 43 条
[31]   A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease [J].
Omland, Torbjorn ;
de Lemos, James A. ;
Sabatine, Marc S. ;
Christophi, Costas A. ;
Rice, Madeline Murguia ;
Jablonski, Kathleen A. ;
Tjora, Solve ;
Domanski, Michael J. ;
Gersh, Bernard J. ;
Rouleau, Jean L. ;
Pfeffer, Marc A. ;
Braunwald, Eugene .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (26) :2538-2547
[32]   Characterization of non-calcified coronary atherosclerotic plaque by multi-detector row CT: Comparison to IVUS [J].
Pohle, Karsten ;
Achenbach, Stephan ;
MacNeill, Briain ;
Ropers, Dieter ;
Ferencik, Maros ;
Moselewski, Fabian ;
Hoffmann, Udo ;
Brady, Thomas J. ;
Jang, Ik-Kyung ;
Daniel, Werner G. .
ATHEROSCLEROSIS, 2007, 190 (01) :174-180
[33]   Smooth muscle cells in human atherosclerotic plaques secrete and proliferate in response to high mobility group box 1 protein [J].
Porto, Annalisa ;
Palumbo, Roberta ;
Pieroni, Maurizio ;
Aprigliano, Gianfranco ;
Chiesa, Roberto ;
Sanvito, Francesca ;
Maseri, Attilio ;
Bianchi, Marco E. .
FASEB JOURNAL, 2006, 20 (14) :2565-+
[34]   Heart disease and stroke statistics - 2007 update - A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee [J].
Rosamond, Wayne ;
Flegal, Katherine ;
Friday, Gary ;
Furie, Karen ;
Go, Alan ;
Greenlund, Kurt ;
Haase, Nancy ;
Ho, Michael ;
Howard, Virginia ;
Kissela, Bret ;
Kittner, Steven ;
Lloyd-Jones, Donald ;
McDermott, Mary ;
Meigs, James ;
Moy, Claudia ;
Nichol, Graham ;
O'Donnell, Christopher J. ;
Roger, Veronique ;
Rumsfeld, John ;
Sorlie, Paul ;
Steinberger, Julia ;
Thom, as Thom ;
Wasserthiel-Smoller, Sylvia ;
Hong, Yuling .
CIRCULATION, 2007, 115 (05) :E69-E171
[35]   Imaging of atherosclerotic cardiovascular disease [J].
Sanz, Javier ;
Fayad, Zahi A. .
NATURE, 2008, 451 (7181) :953-957
[36]   Angiogenetic signaling through hypoxia -: HMGB1:: An angiogenetic switch molecule [J].
Schlueter, C ;
Weber, H ;
Meyer, B ;
Rogalla, P ;
Röser, K ;
Hauke, S ;
Bullerdiek, J .
AMERICAN JOURNAL OF PATHOLOGY, 2005, 166 (04) :1259-1263
[37]   Receptor for advanced glycation end products (RAGE) deficiency attenuates the development of atherosclerosis in diabetes [J].
Soro-Paavonen, Aino ;
Watson, Anna M. D. ;
Li, Jiaze ;
Paavonen, Karri ;
Koitka, Audrey ;
Calkin, Anna C. ;
Barit, David ;
Coughlan, Melinda T. ;
Drew, Brian G. ;
Lancaster, Graeme I. ;
Thomas, Merlin ;
Forbes, Josephine M. ;
Nawroth, Peter P. ;
Bierhaus, Angelika ;
Cooper, Mark E. ;
Jandeleit-Dahm, Karin A. .
DIABETES, 2008, 57 (09) :2461-2469
[38]   The Role of HMGB1/RAGE in Inflammatory Cardiomyopathy [J].
Volz, Hans C. ;
Kaya, Ziya ;
Katus, Hugo A. ;
Andrassy, Martin .
SEMINARS IN THROMBOSIS AND HEMOSTASIS, 2010, 36 (02) :185-194
[39]   Extracellular role of HMGB1 in inflammation and sepsis [J].
Wang, H ;
Yang, H ;
Tracey, KJ .
JOURNAL OF INTERNAL MEDICINE, 2004, 255 (03) :320-331
[40]   Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data [J].
Wensley, Frances ;
Gao, Pei ;
Burgess, Stephen ;
Kaptoge, Stephen ;
Di Angelantonio, Emanuele ;
Shah, Tina ;
Engert, James C. ;
Clarke, Robert ;
Davey-Smith, George ;
Nordestgaard, Borge G. ;
Saleheen, Danish ;
Samani, Nilesh J. ;
Sandhu, Manjinder ;
Anand, Sonia ;
Pepys, Mark B. ;
Smeeth, Liam ;
Whittaker, John ;
Casas, Juan Pablo ;
Thompson, Simon G. ;
Hingorani, Aroon D. ;
Danesh, John ;
Eiriksdottir, G. ;
Harris, T. B. ;
Launer, L. J. ;
Gudnason, V. ;
Folsom, A. R. ;
Andrews, G. ;
Ballantyne, C. M. ;
Samani, N. J. ;
Hall, A. S. ;
Braund, P. S. ;
Balmforth, A. J. ;
Whincup, P. H. ;
Morris, R. ;
Lawlor, D. A. ;
Lowe, G. D. O. ;
Timpson, N. ;
Ebrahim, S. ;
Ben-Shlomo, Y. ;
Davey-Smith, G. ;
Timpson, N. ;
Nordestgaard, B. G. ;
Tybjaerg-Hansen, A. ;
Zacho, J. ;
Brown, M. ;
Sandhu, M. ;
Ricketts, S. L. ;
Ashford, S. ;
Lange, L. ;
Reiner, A. .
BRITISH MEDICAL JOURNAL, 2011, 342 :425