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Endothelial cell is critical in HMGB1 mediated cardiac impairment in ischemic heart disease
International Journal of Cardiology 187 (2015) 39–40
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Endothelial cell is critical in HMGB1 mediated cardiac impairment in ischemic heart disease☆ Zhaowei Zhu, Xinqun Hu, Zhenfei Fang, Shenghua Zhou ⁎ Department of Cardiology, Second Xiangya Hospital of Central South University, Changsha, PR China
a r t i c l e
i n f o
Article history: Received 19 March 2015 Accepted 21 March 2015 Available online 24 March 2015 Keywords: HMGB1 Endothelial cells Ischemic heart disease
Dear Editor: We have recently read with great interest the clinical report by Liu T and colleagues [1] concerning “Increased serum HMGB1 level may predict the fatal outcomes in patients with chronic heart failure”. They indicate that serum HMGB1 levels were inversely correlated with LVEF and positively correlated with NT-pro-BNP and may be an alternative indicator in the risk stratification of patients with chronic HF (heart failure). In this paper, although the authors come to a conclusion that serum HMGB1 levels were correlated with the risk stratification of patients with chronic HF, the exact mechanisms are totally unknown. Besides, the enrolled 94 patients are all due to ischemic cardiomyopathy, it actually provides a link between HMGB1 and ischemic heart disease. Here we propose that endothelial cells may mediate the effect of HMGB1 in ischemic heart disease. The reasons are as follows. First of all, it has been confirmed that serum HMGB1 level increased in ischemic or ischemic–reperfusion heart disease and even correlated with the severity of coronary artery stenosis in patients with coronary artery disease [2,3], which provided strong clinical evidences for the role of HMGB1 in ischemic heart disease. Secondly, Lin et al. [4] investigated the role of HMGB1 with a rat myocardial I/R model. They found that I/R resulted in a 4.8-fold increase in HMGB1 expression with an impaired cardiac function compared with the sham group. In addition inhibiting the elevated HMGB1 level could ☆ Authorship statement: all of the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Department of Cardiology, Second Xiangya Hospital of Central South University, Middle Ren-Min Road No. 139, Changsha, Hunan 410011, PR China. E-mail address: [email protected] (S. Zhou).
http://dx.doi.org/10.1016/j.ijcard.2015.03.342 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
alleviate impaired cardiac function. The work mentioned above is consistent with the clinical research from Liu and indicates a bad effect of HMGB1 in ischemic heart disease. Thirdly, HMGB1, as a non-chromosomal nuclear protein, could be negatively released by necrotic cell and apoptotic cell or positively activated by innate immune cells (such as macrophages and monocytes) [5, 6]. Recently even endothelial cell has been found to release HMGB1 under certain conditions like hypoxia, which indicate a potential role of HMGB1 in endothelial cells [7]. Indeed, HMGB1 can promote angiogenesis in vitro and in vivo [8], and can also inhibit the migration of endothelial cells. Actually, to some extent, the suppressed migration of endothelial cells may account for the bad effects of HMGB1 in ischemic heart disease. However, recently, we found that HMGB1 can impair endothelial cell function by increasing the permeability of endothelial cells through TLR4/caveolin-1 pathway [9], which gives us a novel insight of HMGB1's role in ischemic heart disease. So the coronary artery endothelial cells or the microcirculation endothelial cells in myocardium from patients of ischemic heart disease could be affected directly by increased serum HMGB1. Subsequently, it is possible that HMGB1 impairs the function of coronary artery endothelial cells and the microcirculation endothelial cells in myocardium at least increase their permeability through TLR4 pathway and increased permeability can promote more cytokines (tumor necrotic factor-α (TNF-α) and the interleukin (IL)-6) migrating to myocardium tissues from microvessel system, which can damage myocardium further. The higher the serum HMGB1 is, the worse the prognosis of ischemic heart disease patients is. This may explain the increased mortality rates in patients with ischemic heart disease in one aspect [3]. So, endothelial cells can be as an important object to research in HMGB1 mediated ischemic heart disease. Besides, HMGB1 is a redox sensitive protein with three cysteine residues at positions 23, 45 and 106. Its activity can be different with different redox states [10]. However, we do not know the exact state of the increased serum HMGB1 in ischemic heart disease, which will bring us difficulties in investigating the specific mechanisms underlying such phenomenon. Thus, the redox state of serum HMGB1 should also be clarified in the future studies, which can help us in knowing this biomarker well. Sources of funding This work was supported in part by the National Natural Science Foundation of China (NSFC) Projects 81270257 (to SHZ) and 81470017 (to XQH).
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Z. Zhu et al. / International Journal of Cardiology 187 (2015) 39–40
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] T. Liu, Y. Zhang, Y.H. Zhou, et al., Increased serum HMGB1 level may predict the fatal outcomes in patients with chronic heart failure, Int. J. Cardiol. 184C (2015) 318–320. [2] X. Hu, H. Jiang, Q. Bai, et al., Increased serum HMGB1 is related to the severity of coronary artery stenosis, Clin. Chim. Acta 406 (2009) 139–142. [3] T. Hashimoto, J. Ishii, F. Kitagawa, et al., Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction, Atherosclerosis 221 (2012) 490–495. [4] Y. Lin, L. Chen, W. Li, J. Fang, Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate, Exp. Ther. Med. 9 (2015) 1537–1541.
[5] C.W. Bell, W. Jiang, C.F. Reich III, D.S. Pisetsky, The extracellular release of HMGB1 during apoptotic cell death, Am. J. Physiol. Cell Physiol. 291 (2006) C1318–C1325. [6] P. Scaffidi, T. Misteli, M.E. Bianchi, Release of chromatin protein HMGB1 by necrotic cells triggers inflammation, Nature 418 (2002) 191–195. [7] E.M. Bauer, R. Shapiro, T.R. Billiar, P.M. Bauer, High mobility group Box 1 inhibits human pulmonary artery endothelial cell migration via a Toll-like receptor 4- and interferon response factor 3-dependent mechanism(s), J. Biol. Chem. 288 (2013) 1365–1373. [8] U. Sachdev, X. Cui, G. Hong, et al., High mobility group box 1 promotes endothelial cell angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury, J. Vasc. Surg. 55 (2012) 180–191. [9] R. Jiang, J. Cai, Z. Zhu, et al., Hypoxic trophoblast HMGB1 induces endothelial cell hyperpermeability via the TRL-4/caveolin-1 pathway, J. Immunol. 193 (2014) 5000–5012. [10] E. Venereau, M. Schiraldi, M. Uguccioni, M.E. Bianchi, HMGB1 and leukocyte migration during trauma and sterile inflammation, Mol. Immunol. 55 (2013) 76–82.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Endothelial cell is critical in HMGB1 mediated cardiac impairment in ischemic heart disease☆ Zhaowei Zhu, Xinqun Hu, Zhenfei Fang, Shenghua Zhou ⁎ Department of Cardiology, Second Xiangya Hospital of Central South University, Changsha, PR China
a r t i c l e
i n f o
Article history: Received 19 March 2015 Accepted 21 March 2015 Available online 24 March 2015 Keywords: HMGB1 Endothelial cells Ischemic heart disease
Dear Editor: We have recently read with great interest the clinical report by Liu T and colleagues [1] concerning “Increased serum HMGB1 level may predict the fatal outcomes in patients with chronic heart failure”. They indicate that serum HMGB1 levels were inversely correlated with LVEF and positively correlated with NT-pro-BNP and may be an alternative indicator in the risk stratification of patients with chronic HF (heart failure). In this paper, although the authors come to a conclusion that serum HMGB1 levels were correlated with the risk stratification of patients with chronic HF, the exact mechanisms are totally unknown. Besides, the enrolled 94 patients are all due to ischemic cardiomyopathy, it actually provides a link between HMGB1 and ischemic heart disease. Here we propose that endothelial cells may mediate the effect of HMGB1 in ischemic heart disease. The reasons are as follows. First of all, it has been confirmed that serum HMGB1 level increased in ischemic or ischemic–reperfusion heart disease and even correlated with the severity of coronary artery stenosis in patients with coronary artery disease [2,3], which provided strong clinical evidences for the role of HMGB1 in ischemic heart disease. Secondly, Lin et al. [4] investigated the role of HMGB1 with a rat myocardial I/R model. They found that I/R resulted in a 4.8-fold increase in HMGB1 expression with an impaired cardiac function compared with the sham group. In addition inhibiting the elevated HMGB1 level could ☆ Authorship statement: all of the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author at: Department of Cardiology, Second Xiangya Hospital of Central South University, Middle Ren-Min Road No. 139, Changsha, Hunan 410011, PR China. E-mail address: [email protected] (S. Zhou).
http://dx.doi.org/10.1016/j.ijcard.2015.03.342 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
alleviate impaired cardiac function. The work mentioned above is consistent with the clinical research from Liu and indicates a bad effect of HMGB1 in ischemic heart disease. Thirdly, HMGB1, as a non-chromosomal nuclear protein, could be negatively released by necrotic cell and apoptotic cell or positively activated by innate immune cells (such as macrophages and monocytes) [5, 6]. Recently even endothelial cell has been found to release HMGB1 under certain conditions like hypoxia, which indicate a potential role of HMGB1 in endothelial cells [7]. Indeed, HMGB1 can promote angiogenesis in vitro and in vivo [8], and can also inhibit the migration of endothelial cells. Actually, to some extent, the suppressed migration of endothelial cells may account for the bad effects of HMGB1 in ischemic heart disease. However, recently, we found that HMGB1 can impair endothelial cell function by increasing the permeability of endothelial cells through TLR4/caveolin-1 pathway [9], which gives us a novel insight of HMGB1's role in ischemic heart disease. So the coronary artery endothelial cells or the microcirculation endothelial cells in myocardium from patients of ischemic heart disease could be affected directly by increased serum HMGB1. Subsequently, it is possible that HMGB1 impairs the function of coronary artery endothelial cells and the microcirculation endothelial cells in myocardium at least increase their permeability through TLR4 pathway and increased permeability can promote more cytokines (tumor necrotic factor-α (TNF-α) and the interleukin (IL)-6) migrating to myocardium tissues from microvessel system, which can damage myocardium further. The higher the serum HMGB1 is, the worse the prognosis of ischemic heart disease patients is. This may explain the increased mortality rates in patients with ischemic heart disease in one aspect [3]. So, endothelial cells can be as an important object to research in HMGB1 mediated ischemic heart disease. Besides, HMGB1 is a redox sensitive protein with three cysteine residues at positions 23, 45 and 106. Its activity can be different with different redox states [10]. However, we do not know the exact state of the increased serum HMGB1 in ischemic heart disease, which will bring us difficulties in investigating the specific mechanisms underlying such phenomenon. Thus, the redox state of serum HMGB1 should also be clarified in the future studies, which can help us in knowing this biomarker well. Sources of funding This work was supported in part by the National Natural Science Foundation of China (NSFC) Projects 81270257 (to SHZ) and 81470017 (to XQH).
40
Z. Zhu et al. / International Journal of Cardiology 187 (2015) 39–40
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] T. Liu, Y. Zhang, Y.H. Zhou, et al., Increased serum HMGB1 level may predict the fatal outcomes in patients with chronic heart failure, Int. J. Cardiol. 184C (2015) 318–320. [2] X. Hu, H. Jiang, Q. Bai, et al., Increased serum HMGB1 is related to the severity of coronary artery stenosis, Clin. Chim. Acta 406 (2009) 139–142. [3] T. Hashimoto, J. Ishii, F. Kitagawa, et al., Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction, Atherosclerosis 221 (2012) 490–495. [4] Y. Lin, L. Chen, W. Li, J. Fang, Role of high-mobility group box-1 in myocardial ischemia/reperfusion injury and the effect of ethyl pyruvate, Exp. Ther. Med. 9 (2015) 1537–1541.
[5] C.W. Bell, W. Jiang, C.F. Reich III, D.S. Pisetsky, The extracellular release of HMGB1 during apoptotic cell death, Am. J. Physiol. Cell Physiol. 291 (2006) C1318–C1325. [6] P. Scaffidi, T. Misteli, M.E. Bianchi, Release of chromatin protein HMGB1 by necrotic cells triggers inflammation, Nature 418 (2002) 191–195. [7] E.M. Bauer, R. Shapiro, T.R. Billiar, P.M. Bauer, High mobility group Box 1 inhibits human pulmonary artery endothelial cell migration via a Toll-like receptor 4- and interferon response factor 3-dependent mechanism(s), J. Biol. Chem. 288 (2013) 1365–1373. [8] U. Sachdev, X. Cui, G. Hong, et al., High mobility group box 1 promotes endothelial cell angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury, J. Vasc. Surg. 55 (2012) 180–191. [9] R. Jiang, J. Cai, Z. Zhu, et al., Hypoxic trophoblast HMGB1 induces endothelial cell hyperpermeability via the TRL-4/caveolin-1 pathway, J. Immunol. 193 (2014) 5000–5012. [10] E. Venereau, M. Schiraldi, M. Uguccioni, M.E. Bianchi, HMGB1 and leukocyte migration during trauma and sterile inflammation, Mol. Immunol. 55 (2013) 76–82.