International Journal of Cardiology 184 (2015) 318–320
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Increased serum HMGB1 level may predict the fatal outcomes in patients with chronic heart failure Tao Liu, De-Yong Zhang, Yan-Hong Zhou, Qian-Feng Han, Lan-Hua Wang, Lei Wu, Heng-Chen Yao ⁎ Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Shandong Province, Liaocheng 252000, China
a r t i c l e
i n f o
Article history: Received 13 January 2015 Accepted 24 February 2015 Available online 25 February 2015 Keywords: Heart failure High mobility group box-1 N terminal pro-brain natriuretic peptide Mortality
A total of 94 patients with chronic heart failure (HF) due to ischemic cardiomyopathy enrolled between Jan. 2009 and Dec. 2011 were included in the study, including 34 patients with New York Heart Association (NYHA) class II, 31 with class III and 29 with class IV. There were no statistically significant differences among the groups in age, gender, hypertension, or diabetics (p N 0.05). Compared with the control group, a higher proportion of patients in the HF group were treated with diuretics, angiotensin converting enzyme inhibitors (ACEIs), betablockers or digoxin (p b 0.05). This study was approved by the Institutional Review Board of Liaocheng People's Hospital. Informed written consent was obtained from all participants. The diagnosis of HF was according to the current guideline and ischemic etiology of HF was assumed in patients with history of definite coronary heart disease, myocardial infarction and/or revascularization. Patients with acute infections or immune systemic diseases, liver and kidney dysfunction, malignant tumors, severe trauma, and surgery within the past 6 months were excluded. Thirty patients with coronary artery disease but normal left ventricular function were also recruited from our hospital as a control group. Echocardiographic examinations were conducted within 24 h after the patients' admission. Serum levels of high mobility group box protein 1 (HMGB1) were assayed by enzyme-linked immunosorbent assay (ELISA) according to the manufactures' instructions (HMGB-1 ELISA kits, Wuhan USCN Sciences Co., Ltd, China). The serum NT-pro-BNP
⁎ Corresponding author. E-mail address: [email protected] (H.-C. Yao).
http://dx.doi.org/10.1016/j.ijcard.2015.02.088 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
level was measured by the electrochemical luminescence method with Luminous instrument Roche Chemistry (E601) (Cobas company, Roche Diagnostics (Shanghai) Co., Ltd, China) in the central pathology laboratory of our hospital. All the participants were followed up bimonthly for a total 12 months at our outpatient clinics. The follow-up protocols were physical examination, 12-lead ECG, and medication review. Continuous variables were presented as mean ± standard deviation, and were compared by two-tail Student's t test or one way analysis of variance (ANOVA) for multiple variables. Categorical data were presented as numbers and percentages, and were compared with Chi-square test or Fisher's exact test. Correlations of serum HMGB1 with other biomarkers were assessed by Pearson's test. All data were analyzed by SPSS 12.0 software (SPSS, Inc. Chicago, IL, USA). A two-sided p value of ≤0.05 was considered to be significant. Serum NT-pro-BNP levels in patients with HF were higher than that in the control group (3941 ± 1962 vs. 189 ± 63 ng/L, p b 0.01). Serum HMBG1 levels in patients with HF were also higher than that in the control group (28.72 ± 6.92 vs. 25.71 ± 4.45 μg/L, p = 0.025). Serum HMBG1 levels in NYHA class IV were higher than in class II (31.39 ± 6.45 vs. 26.33 ± 7.84 μg/L, p b 0.002) (As shown in Tables 1 and 2).
Fig. 1. Correlations between serum HMGB1 and LVEF. HMGB1: high-mobility group box 1; LVEF: left ventricular ejection fraction.
T. Liu et al. / International Journal of Cardiology 184 (2015) 318–320
Fig. 2. Correlations between serum HMGB1 and NT-pro-BNP. HMGB1: high-mobility group box 1; NT-pro-BNP: N-terminal pro-B-type natriuretic peptide.
Table 1 Baseline characteristics of the group patients. Variables
Age Male Hypertension Diabetics Prior MI Medications Diuretics ACEI Beta-blockers Digoxin Statins
NYHA functional class in ICM
Control (n = 30)
II (n = 34)
III (n = 31)
IV (n = 29)
66.8 ± 12.9 15 (44.1) 5 (14.7) 3 (8.8) 3 (8.8)
65.4 ± 8.7 20 (64.5) 6 (19.4) 6 (19.4) 5 (16.1)
59.2 ± 10.6 22 (75.9) 5 (17.2) 3 (10.3) 6 (20.7)⁎
69.3 ± 12.7 17 (56.7) 7 (23.3) 5 (16.7) 1 (3.3)
6 (17.6) 8 (23.5) 23 (67.6)⁎ 4 (11.8) 15 (44.1)
18 (58.1)⁎ 16 (51.6)⁎ 17 (54.8)⁎ 23 (74.2)⁎ 18 (58.1)
23 (79.3)⁎ 21 (72.4)⁎ 9 (31.0)⁎ 26 (89.7)⁎ 20 (69.0)
0 5 (16.7) 4 (13.3) 0 17 (56.7)
Data are present as mean ± S.D. or n (%). ICM, ischemic cardiomyopathy; MI, myocardial infarction; ACEI, angiotensin converting enzyme inhibitor. ⁎ p b 0.05 vs. control.
The serum HMGB1 levels were positively correlated with NT-pro-BNP (r = 0.440, p b 0.01), but was inversely correlated with LVEF (r = −0.280, p b 0.01). After a 12-month follow-up, 5 patients (5.1%) in the HF group died. Serum HMGB1 levels in patients who died were higher than in the survivors (38.03 ± 2.96 vs. 28.26 ± 6.72 μg/L, p = 0.002). Increased serum HMGB1 level was an independent predictor for death (OR: 1.421, 95% CI: 1.091–1.852). In the control group, no patients developed heart failure or died at the end of the 12-month followup.
319
HMGB1 is one of the most important non-histone proteins in the eukaryotic nuclei. HMGB1, which is composed of 215 residues and divided into two DNA-binding domains (A box and B box) and a negative C-terminus, is widely distributed in the liver, brain, spleen, lung, heart, kidney and lymphatic tissue [1,2]. The first 40 peptide segments of B-box, which are the effective pro-inflammatory cytokine area of HMGB1, can induce the production of tumor necrotic factor-α (TNFα) and the interleukin (IL)-6 [1]. HMGB1 is derived from necrotic cells and bound with its corresponding receptor after activating monocytes/ macrophages. It is then acted as an important mediator of inflammation to promote tissue repair and regeneration [3]. HMGB1 plays a key role in many cardiovascular diseases, such as atherosclerosis, myocardial ischemia/reperfusion injuries, heart failure and myocardial infarction [4–9]. Heart failure is the end stage of a variety of heart disease, with a high mortality and morbidity. A variety of inflammatory cytokines such as IL1β, IL-6 and TNF-α can be involved in the occurrence and development process of HF [10,11]. Recent studies have shown that serum HMGB1 is increased in patients with HF and levels of HMGB1 were correlated with worsen ventricular function [12,13]. However, the role of HMGB1 in predicting the prognosis of HF is not clear. In this study, we measured serum HMGB1 in patients with chronic HF and evaluated the role of this biomarker in the prognosis of these patients. Experimental studies showed that administration of HMGB1 impaired the cardiac function following myocardial infarction [14]. HMGB1 can aggravate the myocardial injury by promoting the amplification of the number of Th17 cells in experimental myocarditis [14]. Specific HMGB1 monoclonal antibodies that block the Th17 cells in local myocardial tissues can reduce the injuries of cardiomyopathy [15]. In consistent with the previous studies, the present study found that serum HMGB1 levels were significantly higher in patients with heart failure. Furthermore, HMGB1 levels were inversely correlated with LVEF, suggesting serum HMGB1 is related to the severity of heart failure in patients with a history of myocardial ischemia. Increased serum HMGB1 levels were an independent predictor for death in patients during a 12-month follow-up. NT-pro-BNP, a definite indicator for heart failure evaluation, is widely used for stratification of chronic HF in sorts of clinical conditions [16]. The present study found that serum HMGB1 levels were positively correlated with NT-pro-BNP. These results indicate that serum HMGB1 levels may be an alternative indicator in the risk stratification of patients with chronic HF. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. (See Figs. 1 and 2).
Conflict of interest None declared.
Table 2 Biochemical results in ICM and the control groups. Variables
NYHA functional class in ICM Total (n = 94)
II (n = 34)
III (n = 31)
IV (n = 29)
HMGB1 (μg/L)
28.78 (6.92) p = 0.025 0.34 (0.06) p b 0.001 3941 (1962) p b 0.001
26.33 (7.84) p = 0.694 0.39 (0.03) p b 0.001 2123 (866) p b 0.001
29.02 (5.35) p = 0.040 0.31 (0.06) p b 0.001 4024 (1033) p b 0.001
31.39 (6.45) p = 0.001 0.30 (0.05) p b 0.001 5983 (1556) p b 0.001
LVEF
NT-pro-BNP (ng/L)
Control (n = 30)
25.71 (4.45) 0.65 (0.06) 189 (63)
Values are means and (SD). ICM, ischemic cardiomyopathy; HMGB1, high-mobility group box 1; LVEF, left ventricular ejection fraction; NT-pro-BNP, N-terminal pro-B-type natriuretic peptide. p values are present as comparison with control.
320
T. Liu et al. / International Journal of Cardiology 184 (2015) 318–320
Acknowledgments This work was supported by the Natural Science Foundation of Shandong Province (No. ZR2013HL017), the Natural Science Foundation of Liaocheng City (2012NS13), and the Science and Technology Developing Project of Liaocheng City (2014GJH26). References [1] J. Li, R. Kokkola, S. Tabibzadeh, R. Yang, M. Ochani, X. Qiang, H.E. Harris, C.J. Czura, H. Wang, L. Ulloa, H. Wang, H.S. Warren, L.L. Moldawer, M.P. Fink, U. Andersson, K.J. Tracey, H. Yang, Structural basis for the proinflammatory cytokine activity of high mobility group box 1, Mol. Med. 9 (2003) 37–45. [2] J.O. Thomas, HMG1 and 2: architectural DNA-binding proteins, Biochem. Soc. Trans. 29 (2001) 395–401. [3] I.E. Dumitriu, P. Baruah, A.A. Manfredi, M.E. Bianchi, P. Rovere-Querini, HMGB1: guiding immunity from within, Trends Immunol. 26 (2005) 381–387. [4] T. Kohno, T. Anzai, K. Naito, T. Miyasho, M. Okamoto, H. Yokota, S. Yamada, Y. Maekawa, T. Takahashi, T. Yoshikawa, A. Ishizaka, S. Ogawa, Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling, Cardiovasc. Res. 81 (2009) 565–573. [5] K. Inoue, K. Kawahara, K.K. Biswas, K. Ando, K. Mitsudo, M. Nobuyoshi, I. Maruyama, HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques, Cardiovasc. Pathol. 16 (2007) 136–143. [6] H.S. Ding, J. Yang, High mobility group box-1 and cardiovascular diseases, Saudi Med J. 31 (2010) 486–489. [7] A.M. Avalos, K. Kiefer, J. Tian, S. Christensen, M. Shlomchik, A.J. Coyle, A. MarshakRothstein, Rage-independent autoreactive B cell activation in response to chromatin and HMGB1/DNA immune complexes, Autoimmunity 43 (2010) 103–110.
[8] H.C. Yao, A.P. Zhao, Q.F. Han, L. Wu, D.K. Yao, L.X. Wang, Correlation between serum high-mobility group box-1 levels and high-sensitivity C-reactive protein and troponin I in patients with coronary artery disease, Exp. Ther. Med. 6 (2013) 121–124. [9] H.C. Yao, L.J. Yang, Q.F. Han, L.H. Wang, L. Wu, C.Y. Zhang, K.L. Tian, M. Zhang, Postconditioning with simvastatin decreases the myocardial injury in rats following acute myocardial ischemia, Exp. Ther. Med. (2015) (accepted, in press). [10] M. Rauchhaus, W. Doehner, D.P. Francis, C. Davos, M. Kemp, C. Liebenthal, J. Niebauer, J. Hooper, H.D. Volk, A.J. Coats, S.D. Anker, Plasma cytokine parameters and mortality in patients with chronic heart failure, Circulation 102 (2000) 3060–3067. [11] A. Deswal, N.J. Petersen, A.M. Feldman, J.B. Young, B.G. White, D.L. Mann, Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the vesnarinone trial (vest), Circulation 103 (2001) 2055–2059. [12] L.J. Wang, L. Lu, F.R. Zhang, Q.J. Chen, R. De Caterina, W.F. Shen, Increased serum highmobility group box-1 and cleaved receptor for advanced glycation endproducts levels and decreased endogenous secretory receptor for advanced glycation endproducts levels in diabetic and non-diabetic patients with heart failure, Eur. J. Heart Fail. 13 (2011) 440–449. [13] H.C. Volz, D. Laohachewin, D. Schellberg, A.R. Wienbrandt, M. Nelles, C. Zugck, Z. Kaya, H.A. Katus, M. Andrassy, HMGB1 is an independent predictor of death and heart transplantation in heart failure, Clin. Res. Cardiol. 101 (2012) 427–435. [14] M. Andrassy, H.C. Volz, J.C. Igwe, B. Funke, S.N. Eichberger, Z. Kaya, S. Buss, F. Autschbach, S.T. Pleger, I.K. Lukic, F. Bea, S.E. Hardt, P.M. Humpert, M.E. Bianchi, H. Mairbäurl, P.P. Nawroth, A. Remppis, H.A. Katus, A. Bierhaus, High-mobility group box-1 in ischemia–reperfusion injury of the heart, Circulation 117 (2008) 3216–3226. [15] Z. Su, C. Sun, C. Zhou, Y. Liu, H. Zhu, S. Sandoghchian, D. Zheng, T. Peng, Y. Zhang, Z. Jiao, S. Wang, H. Xu, HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses TH17-cell expansion, Eur. J. Immunol. 41 (2011) 3586–3595. [16] M.R. Cowie, A.D. Struthers, D.A. Wood, A.J. Coats, S.G. Thompson, P.A. Poole-Wilson, G.C. Sutton, Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care, Lancet 350 (1997) 1349–1353.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Increased serum HMGB1 level may predict the fatal outcomes in patients with chronic heart failure Tao Liu, De-Yong Zhang, Yan-Hong Zhou, Qian-Feng Han, Lan-Hua Wang, Lei Wu, Heng-Chen Yao ⁎ Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Shandong Province, Liaocheng 252000, China
a r t i c l e
i n f o
Article history: Received 13 January 2015 Accepted 24 February 2015 Available online 25 February 2015 Keywords: Heart failure High mobility group box-1 N terminal pro-brain natriuretic peptide Mortality
A total of 94 patients with chronic heart failure (HF) due to ischemic cardiomyopathy enrolled between Jan. 2009 and Dec. 2011 were included in the study, including 34 patients with New York Heart Association (NYHA) class II, 31 with class III and 29 with class IV. There were no statistically significant differences among the groups in age, gender, hypertension, or diabetics (p N 0.05). Compared with the control group, a higher proportion of patients in the HF group were treated with diuretics, angiotensin converting enzyme inhibitors (ACEIs), betablockers or digoxin (p b 0.05). This study was approved by the Institutional Review Board of Liaocheng People's Hospital. Informed written consent was obtained from all participants. The diagnosis of HF was according to the current guideline and ischemic etiology of HF was assumed in patients with history of definite coronary heart disease, myocardial infarction and/or revascularization. Patients with acute infections or immune systemic diseases, liver and kidney dysfunction, malignant tumors, severe trauma, and surgery within the past 6 months were excluded. Thirty patients with coronary artery disease but normal left ventricular function were also recruited from our hospital as a control group. Echocardiographic examinations were conducted within 24 h after the patients' admission. Serum levels of high mobility group box protein 1 (HMGB1) were assayed by enzyme-linked immunosorbent assay (ELISA) according to the manufactures' instructions (HMGB-1 ELISA kits, Wuhan USCN Sciences Co., Ltd, China). The serum NT-pro-BNP
⁎ Corresponding author. E-mail address: [email protected] (H.-C. Yao).
http://dx.doi.org/10.1016/j.ijcard.2015.02.088 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
level was measured by the electrochemical luminescence method with Luminous instrument Roche Chemistry (E601) (Cobas company, Roche Diagnostics (Shanghai) Co., Ltd, China) in the central pathology laboratory of our hospital. All the participants were followed up bimonthly for a total 12 months at our outpatient clinics. The follow-up protocols were physical examination, 12-lead ECG, and medication review. Continuous variables were presented as mean ± standard deviation, and were compared by two-tail Student's t test or one way analysis of variance (ANOVA) for multiple variables. Categorical data were presented as numbers and percentages, and were compared with Chi-square test or Fisher's exact test. Correlations of serum HMGB1 with other biomarkers were assessed by Pearson's test. All data were analyzed by SPSS 12.0 software (SPSS, Inc. Chicago, IL, USA). A two-sided p value of ≤0.05 was considered to be significant. Serum NT-pro-BNP levels in patients with HF were higher than that in the control group (3941 ± 1962 vs. 189 ± 63 ng/L, p b 0.01). Serum HMBG1 levels in patients with HF were also higher than that in the control group (28.72 ± 6.92 vs. 25.71 ± 4.45 μg/L, p = 0.025). Serum HMBG1 levels in NYHA class IV were higher than in class II (31.39 ± 6.45 vs. 26.33 ± 7.84 μg/L, p b 0.002) (As shown in Tables 1 and 2).
Fig. 1. Correlations between serum HMGB1 and LVEF. HMGB1: high-mobility group box 1; LVEF: left ventricular ejection fraction.
T. Liu et al. / International Journal of Cardiology 184 (2015) 318–320
Fig. 2. Correlations between serum HMGB1 and NT-pro-BNP. HMGB1: high-mobility group box 1; NT-pro-BNP: N-terminal pro-B-type natriuretic peptide.
Table 1 Baseline characteristics of the group patients. Variables
Age Male Hypertension Diabetics Prior MI Medications Diuretics ACEI Beta-blockers Digoxin Statins
NYHA functional class in ICM
Control (n = 30)
II (n = 34)
III (n = 31)
IV (n = 29)
66.8 ± 12.9 15 (44.1) 5 (14.7) 3 (8.8) 3 (8.8)
65.4 ± 8.7 20 (64.5) 6 (19.4) 6 (19.4) 5 (16.1)
59.2 ± 10.6 22 (75.9) 5 (17.2) 3 (10.3) 6 (20.7)⁎
69.3 ± 12.7 17 (56.7) 7 (23.3) 5 (16.7) 1 (3.3)
6 (17.6) 8 (23.5) 23 (67.6)⁎ 4 (11.8) 15 (44.1)
18 (58.1)⁎ 16 (51.6)⁎ 17 (54.8)⁎ 23 (74.2)⁎ 18 (58.1)
23 (79.3)⁎ 21 (72.4)⁎ 9 (31.0)⁎ 26 (89.7)⁎ 20 (69.0)
0 5 (16.7) 4 (13.3) 0 17 (56.7)
Data are present as mean ± S.D. or n (%). ICM, ischemic cardiomyopathy; MI, myocardial infarction; ACEI, angiotensin converting enzyme inhibitor. ⁎ p b 0.05 vs. control.
The serum HMGB1 levels were positively correlated with NT-pro-BNP (r = 0.440, p b 0.01), but was inversely correlated with LVEF (r = −0.280, p b 0.01). After a 12-month follow-up, 5 patients (5.1%) in the HF group died. Serum HMGB1 levels in patients who died were higher than in the survivors (38.03 ± 2.96 vs. 28.26 ± 6.72 μg/L, p = 0.002). Increased serum HMGB1 level was an independent predictor for death (OR: 1.421, 95% CI: 1.091–1.852). In the control group, no patients developed heart failure or died at the end of the 12-month followup.
319
HMGB1 is one of the most important non-histone proteins in the eukaryotic nuclei. HMGB1, which is composed of 215 residues and divided into two DNA-binding domains (A box and B box) and a negative C-terminus, is widely distributed in the liver, brain, spleen, lung, heart, kidney and lymphatic tissue [1,2]. The first 40 peptide segments of B-box, which are the effective pro-inflammatory cytokine area of HMGB1, can induce the production of tumor necrotic factor-α (TNFα) and the interleukin (IL)-6 [1]. HMGB1 is derived from necrotic cells and bound with its corresponding receptor after activating monocytes/ macrophages. It is then acted as an important mediator of inflammation to promote tissue repair and regeneration [3]. HMGB1 plays a key role in many cardiovascular diseases, such as atherosclerosis, myocardial ischemia/reperfusion injuries, heart failure and myocardial infarction [4–9]. Heart failure is the end stage of a variety of heart disease, with a high mortality and morbidity. A variety of inflammatory cytokines such as IL1β, IL-6 and TNF-α can be involved in the occurrence and development process of HF [10,11]. Recent studies have shown that serum HMGB1 is increased in patients with HF and levels of HMGB1 were correlated with worsen ventricular function [12,13]. However, the role of HMGB1 in predicting the prognosis of HF is not clear. In this study, we measured serum HMGB1 in patients with chronic HF and evaluated the role of this biomarker in the prognosis of these patients. Experimental studies showed that administration of HMGB1 impaired the cardiac function following myocardial infarction [14]. HMGB1 can aggravate the myocardial injury by promoting the amplification of the number of Th17 cells in experimental myocarditis [14]. Specific HMGB1 monoclonal antibodies that block the Th17 cells in local myocardial tissues can reduce the injuries of cardiomyopathy [15]. In consistent with the previous studies, the present study found that serum HMGB1 levels were significantly higher in patients with heart failure. Furthermore, HMGB1 levels were inversely correlated with LVEF, suggesting serum HMGB1 is related to the severity of heart failure in patients with a history of myocardial ischemia. Increased serum HMGB1 levels were an independent predictor for death in patients during a 12-month follow-up. NT-pro-BNP, a definite indicator for heart failure evaluation, is widely used for stratification of chronic HF in sorts of clinical conditions [16]. The present study found that serum HMGB1 levels were positively correlated with NT-pro-BNP. These results indicate that serum HMGB1 levels may be an alternative indicator in the risk stratification of patients with chronic HF. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. (See Figs. 1 and 2).
Conflict of interest None declared.
Table 2 Biochemical results in ICM and the control groups. Variables
NYHA functional class in ICM Total (n = 94)
II (n = 34)
III (n = 31)
IV (n = 29)
HMGB1 (μg/L)
28.78 (6.92) p = 0.025 0.34 (0.06) p b 0.001 3941 (1962) p b 0.001
26.33 (7.84) p = 0.694 0.39 (0.03) p b 0.001 2123 (866) p b 0.001
29.02 (5.35) p = 0.040 0.31 (0.06) p b 0.001 4024 (1033) p b 0.001
31.39 (6.45) p = 0.001 0.30 (0.05) p b 0.001 5983 (1556) p b 0.001
LVEF
NT-pro-BNP (ng/L)
Control (n = 30)
25.71 (4.45) 0.65 (0.06) 189 (63)
Values are means and (SD). ICM, ischemic cardiomyopathy; HMGB1, high-mobility group box 1; LVEF, left ventricular ejection fraction; NT-pro-BNP, N-terminal pro-B-type natriuretic peptide. p values are present as comparison with control.
320
T. Liu et al. / International Journal of Cardiology 184 (2015) 318–320
Acknowledgments This work was supported by the Natural Science Foundation of Shandong Province (No. ZR2013HL017), the Natural Science Foundation of Liaocheng City (2012NS13), and the Science and Technology Developing Project of Liaocheng City (2014GJH26). References [1] J. Li, R. Kokkola, S. Tabibzadeh, R. Yang, M. Ochani, X. Qiang, H.E. Harris, C.J. Czura, H. Wang, L. Ulloa, H. Wang, H.S. Warren, L.L. Moldawer, M.P. Fink, U. Andersson, K.J. Tracey, H. Yang, Structural basis for the proinflammatory cytokine activity of high mobility group box 1, Mol. Med. 9 (2003) 37–45. [2] J.O. Thomas, HMG1 and 2: architectural DNA-binding proteins, Biochem. Soc. Trans. 29 (2001) 395–401. [3] I.E. Dumitriu, P. Baruah, A.A. Manfredi, M.E. Bianchi, P. Rovere-Querini, HMGB1: guiding immunity from within, Trends Immunol. 26 (2005) 381–387. [4] T. Kohno, T. Anzai, K. Naito, T. Miyasho, M. Okamoto, H. Yokota, S. Yamada, Y. Maekawa, T. Takahashi, T. Yoshikawa, A. Ishizaka, S. Ogawa, Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling, Cardiovasc. Res. 81 (2009) 565–573. [5] K. Inoue, K. Kawahara, K.K. Biswas, K. Ando, K. Mitsudo, M. Nobuyoshi, I. Maruyama, HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques, Cardiovasc. Pathol. 16 (2007) 136–143. [6] H.S. Ding, J. Yang, High mobility group box-1 and cardiovascular diseases, Saudi Med J. 31 (2010) 486–489. [7] A.M. Avalos, K. Kiefer, J. Tian, S. Christensen, M. Shlomchik, A.J. Coyle, A. MarshakRothstein, Rage-independent autoreactive B cell activation in response to chromatin and HMGB1/DNA immune complexes, Autoimmunity 43 (2010) 103–110.
[8] H.C. Yao, A.P. Zhao, Q.F. Han, L. Wu, D.K. Yao, L.X. Wang, Correlation between serum high-mobility group box-1 levels and high-sensitivity C-reactive protein and troponin I in patients with coronary artery disease, Exp. Ther. Med. 6 (2013) 121–124. [9] H.C. Yao, L.J. Yang, Q.F. Han, L.H. Wang, L. Wu, C.Y. Zhang, K.L. Tian, M. Zhang, Postconditioning with simvastatin decreases the myocardial injury in rats following acute myocardial ischemia, Exp. Ther. Med. (2015) (accepted, in press). [10] M. Rauchhaus, W. Doehner, D.P. Francis, C. Davos, M. Kemp, C. Liebenthal, J. Niebauer, J. Hooper, H.D. Volk, A.J. Coats, S.D. Anker, Plasma cytokine parameters and mortality in patients with chronic heart failure, Circulation 102 (2000) 3060–3067. [11] A. Deswal, N.J. Petersen, A.M. Feldman, J.B. Young, B.G. White, D.L. Mann, Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the vesnarinone trial (vest), Circulation 103 (2001) 2055–2059. [12] L.J. Wang, L. Lu, F.R. Zhang, Q.J. Chen, R. De Caterina, W.F. Shen, Increased serum highmobility group box-1 and cleaved receptor for advanced glycation endproducts levels and decreased endogenous secretory receptor for advanced glycation endproducts levels in diabetic and non-diabetic patients with heart failure, Eur. J. Heart Fail. 13 (2011) 440–449. [13] H.C. Volz, D. Laohachewin, D. Schellberg, A.R. Wienbrandt, M. Nelles, C. Zugck, Z. Kaya, H.A. Katus, M. Andrassy, HMGB1 is an independent predictor of death and heart transplantation in heart failure, Clin. Res. Cardiol. 101 (2012) 427–435. [14] M. Andrassy, H.C. Volz, J.C. Igwe, B. Funke, S.N. Eichberger, Z. Kaya, S. Buss, F. Autschbach, S.T. Pleger, I.K. Lukic, F. Bea, S.E. Hardt, P.M. Humpert, M.E. Bianchi, H. Mairbäurl, P.P. Nawroth, A. Remppis, H.A. Katus, A. Bierhaus, High-mobility group box-1 in ischemia–reperfusion injury of the heart, Circulation 117 (2008) 3216–3226. [15] Z. Su, C. Sun, C. Zhou, Y. Liu, H. Zhu, S. Sandoghchian, D. Zheng, T. Peng, Y. Zhang, Z. Jiao, S. Wang, H. Xu, HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses TH17-cell expansion, Eur. J. Immunol. 41 (2011) 3586–3595. [16] M.R. Cowie, A.D. Struthers, D.A. Wood, A.J. Coats, S.G. Thompson, P.A. Poole-Wilson, G.C. Sutton, Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care, Lancet 350 (1997) 1349–1353.
