- Email: [email protected]
Heme oxygenase-1: An important therapeutic target for protecting against myocardial ischemia and reperfusion injury
Letters to the Editor
References [1] Rothblat GH, Phillips MC. High-density lipoprotein heterogeneity and function in reverse cholesterol transport. Curr Opin Lipidol 2010;21:229–38. [2] Tardif JC, Gregoire J, L'Allier PL, et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 2007;297:1675–82. [3] Kim JS, Kang Y, Son KH, Choi SM, Kim KY. Manufacturing and shelf stability of reconstituted high-density lipoprotein for infusion therapy. Biotechnol Bioprocess Eng 2011;16:785–92. [4] Choudhury RP, Rong JX, Trogan E, et al. High-density lipoproteins retard the progression of atherosclerosis and favorably remodel lesions without suppressing indices of inflammation or oxidation. Arterioscler Thromb Vasc Biol 2004;24:1904–9.
587
[5] Michel JB. Anoikis in the cardiovascular system: known and unknown extracellular mediators. Arterioscler Thromb Vasc Biol 2003;23:2146–54. [6] Park HK, Park EC, Bae SW, et al. Expression of heat shock protein 27 in human atherosclerotic plaques and increased plasma level of heat shock protein 27 in patients with acute coronary syndrome. Circulation 2006;114:886–93. [7] Hedges JC, Dechert MA, Yamboliev IA, et al. A role for p38(MAPK)/HSP27 pathway in smooth muscle cell migration. J Biol Chem 1999;274:24211–9. [8] Martin-Ventura JL, Duran MC, Blanco-Colio LM, et al. Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of atherosclerosis. Circulation 2004;110:2216–9.
0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2012.09.226
Heme oxygenase-1: An important therapeutic target for protecting against myocardial ischemia and reperfusion injury Xiaorong Hu 1, Jichun Wang 1, Hong Jiang ⁎ Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
a r t i c l e
i n f o
Article history: Received 8 September 2012 Accepted 29 September 2012 Available online 18 October 2012 Keywords: Myocardial ischemia Reperfusion Heme oxygenase-1 Cardioprotectoion
Myocardial reperfusion therapy (such as thrombolysis and percutaneous coronary intervention) is the optimal therapeutic strategy for acute myocardial infarction, which could preserve myocardial viability and function by reversing myocardial ischemia and reducing the infarct size and has been endorsed in clinical practice [1]. However, the subsequent ischemia and reperfusion (I/R) injury may attenuate the therapeutic benefit [1]. Although reperfusion therapy is essential for the survival of ischemic tissue, reperfusion itself could cause additional cellular injury. I/R could cause local myocardial inflammation, accompanying with apoptosis, which could result in myocardial cell damage [2]. High mobility group box 1 protein (HMGB1), a highly conserved nuclear protein that could regulate gene transcription and maintain the nucleosome structure, could be passively released from necrotic cell, apoptotic cell or actively secreted by innate immune cells (such as macrophages and monocytes) [3,4]. Present study shows that HMGB1 functions as a novel pro-inflammatory cytokine and promotes the progress of myocardial I/R injury [5]. HMGB1 could promote the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), whereas HMGB1 A box peptide (a specific HMGB1 antagonist) could reduce myocardial ischemia and reperfusion injury and inhibit the release of TNF-α and IL-6 [5], indicating that inhibiting HMGB1 expression could ⁎ Corresponding author at: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, China. Tel.: + 86 27 88041911; fax: + 86 27 88040334. E-mail address: [email protected] (H. Jiang). 1 These authors contributed equally to this study as co-first author.
suppress the inflammatory process. Meanwhile, lots of drugs have been found to reduce myocardial I/R injury by inhibiting HMGB1 expression, including asperosaponin X [6], minocycline [7], ethyl pyruvate [8], etc. These suggested that HMGB1 may be a potential therapeutic target for myocardial I/R injury and inhibiting HMGB1 could reduce myocardial I/R injury [9]. Heme oxygenase-1 (HO-1), an inducible isoform of heme oxygenase (HO) enzymes, has been proved that it involves inhibition of early pro-inflammatory cytokines, such as TNF-α and IL-6 which could promote cell apoptosis, and induction of the anti-inflammatory cytokine- (IL-10) which could inhibit cell apoptosis [10,11]. Recently, Liu et al. [12] showed that hydroxysafflor yellow A could provide a protective effect on anoxia/reoxygenation (same as I/R) -induced apoptosis and injury in H9c2 cardiomyocytes and upregulate expression and activity of HO-1, while an HO-1 inhibitor could completely suppress HO-1 enzymatic activity upregulated by hydroxysafflor yellow A and notably diminished the anti-apoptotic effect of hydroxysafflor yellow A, indicating that HO-1 may play an important protective effect on anoxia/reoxygenation or I/R injury. In addition, Takamiya et al. [13] have demonstrated that the circulating levels of HMGB1 were higher in HO-1−/− mice than HO-1+/+ mice and the HO-1−/− mice given HMGB1 neutralizing antibody showed improvement in survival compared with littermates receiving control antibody. In addition, the HO-1 induction has also been shown that it could prevent the release of HMGB1 inendotoxin-activated macrophages in vitro and septic animals in vivo [14]. These results suggested that the HO-1 induction plays an important role in anti-inflammatory effect and could prevent anoxia/reoxygenation or I/R injury by inhibiting HMGB1 release. In conclusion, upregulating HO-1 expression may provide a protective effect on myocardial I/R injury which may be associated with inhibiting HMGB1 expression; HO-1 may be an important therapeutic target for protecting against myocardial I/R injury. This study was partially supported by a grant from the National Natural Science Foundation of China (No. 81100146), grant 111023 from the Fundamental Research Funds for the Central Universities and the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20110141120060). The authors of this manuscript have also certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
588
Letters to the Editor
References [1] Takemura G, Nakagawa M, Kanamori H, et al. Benefits of reperfusion beyond infarction size limitation. Cardiovasc Res 2009;83:269–76. [2] Frangoginis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res 2002;53:31–47. [3] Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002;418:191–5. [4] Bell CW, Jiang W, Reich CF, et al. The extracellular release of HMGB1 during apoptotic cell death. Am J Physiol Cell Physiol 2006;291:C1318–25. [5] Andrassy M, Volz HC, Igwe JC, et al. High-mobility group box-1 in ischemia– reperfusion injury of the heart. Circulation 2008;117:3216–26. [6] Jiang WL, Zhang SP, Zhu HB, et al. Cardioprotection of asperosaponin X on experimental myocardial ischemia injury. Int J Cardiol 2012;155:430–6. [7] Hu X, Zhou X, Xu C, et al. Minocycline protects against myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats. Eur J Pharmacol 2011;654:274–9. [8] Hu X, Cui B, Zhou X, et al. Ethyl pyruvate reduces myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats. Mol Biol Rep 2012;19:227–31.
[9] Hu X, Fu W, Jiang H. HMGB1: a potential therapeutic target for myocardial ischemia and reperfusion injury. Int J Cardiol 2012;155:489-489. [10] Abraham NG, Kappas A. Heme oxygenase and the cardiovascular-renal system. Free Radic Biol Med 2005;39:1–25. [11] Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 2006;86:583–650. [12] Liu SX, Zhang Y, Wang YF, et al. Upregulating of heme oxyenase-1 expression by hydroxysafflor yellow A conferring protection from anoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes. Int J Cardiol 2012;160:95–101. [13] Takamiya R, Hung CC, Hall SR, et al. High-mobility group box 1 contributes to lethality of endotoxemia in heme oxygenase-1-deficient mice. Am J Respir Cell Mol Biol 2009;41:129–35. [14] Tsoyi K, Lee TY, Lee YS, et al. Heme-oxygenase-1 induction and carbon monoxidereleasing molecule inhibit lipopolysaccharide (LPS)-induced high-mobility group box 1 release in vitro and improve survival of mice in LPS- and cecal ligation and punctureinduced sepsis model in vivo. Mol Pharmacol 2009;76:173–82.
0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2012.09.225
Cryoenergy is effective in the treatment of resistant hypertension in non-responders to radiofrequency renal denervation Dirk Prochnau ⁎,1, Hans R. Figulla 1, Ralf Surber 1 Department of Internal Medicine I, Friedrich Schiller University, Jena, Germany
a r t i c l e
i n f o
Article history: Received 7 September 2012 Accepted 29 September 2012 Available online 23 October 2012 Keywords: Resistant hypertension Renal denervation Cryoenergy Non-responders Radiofrequency
in a sheep model [4]. In this animal model, an almost total loss of neurofilaments in the created lesions was observed representing a surrogate marker for effective sympathetic denervation [4]. Here we describe for the first time that cryoablation, as second-line therapy for sympathetic denervation of the renal arteries, is safe and effective in patients with ongoing resistant HTN despite optimized medical treatment and previous unsuccessful RDN with RF current. In this pilot study, three patients with drug resistant hypertension (from a population with a responder rate of 80% [5]) who did not show the intended treatment goal with RF current (reduction of the mean 24h ambulatory BP≥ 10 mm Hg) underwent cryoablation for RDN. One patient with end stage renal disease (ERSD) was successfully treated initially with RF ablation of the renal artery. Twelve months later,
To the Editor, Percutaneous catheter-based renal denervation (RDN) is a new treatment option for drug-resistant hypertension (HTN) [1,2]. Until now, radiofrequency (RF) current is the predominant energy source used for ablation of the renal nerves. However, according to the literature, about 15–20% of treated patients are non-responders to the RDN therapy, indicated by a post-interventional reduction of systolic blood pressure (BP) less than 10 mm Hg [1,2]. In the treatment of cardiac arrhythmias, it was shown that the use of cryoenergy, in comparison to RF current, is accompanied by a reduction of pain and discomfort during ablation without significant differences in the rate of effectiveness [3]. Consequently, this approach might also be used for RDN in drug resistant hypertension to reduce the pain during the procedure, achieve a more effective RDN and minimize the number of non-responders. Recently, we demonstrated that cryoablation of the renal artery is feasible and safe
⁎ Corresponding author at: Department of Internal Medicine I, Friedrich Schiller University, Erlanger Allee 101, 07740 Jena, Germany. Tel.: +49 3641 9324541; fax: +49 3641 9324102. E-mail address: [email protected] (D. Prochnau). 1 All three authors contributed equally to this work.
Table 1 Baseline patient characteristics. Parameter
Patient 1
Patient 2
Patient 3
Sex Age (yr) Time after renal denervation with RF current (months) Comorbidity Diabetes mellitus CAD Chronic renal insufficiency (creatinine N 130 μmol/l) Obstructive sleep apnoea (treated) Body mass index Number of antihypertensive medication Baseline Changes at three-month follow-up 24-h ABPM (mm Hg) Baseline At 1 month At 3 months
Male 38 12
Male 70 4
Male 48 4
− − +
+ + +
− − −
− 18.0
+ 47.5
+ 31.8
6 −3
7 −2
5 No change
189/115 104/63 106/66
154/81 132/73 132/69
187/104 128/88 161/100
Yr, years; RF, radiofrequency; CAD, coronary artery disease; ABPM, ambulatory blood pressure monitoring.
References [1] Rothblat GH, Phillips MC. High-density lipoprotein heterogeneity and function in reverse cholesterol transport. Curr Opin Lipidol 2010;21:229–38. [2] Tardif JC, Gregoire J, L'Allier PL, et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 2007;297:1675–82. [3] Kim JS, Kang Y, Son KH, Choi SM, Kim KY. Manufacturing and shelf stability of reconstituted high-density lipoprotein for infusion therapy. Biotechnol Bioprocess Eng 2011;16:785–92. [4] Choudhury RP, Rong JX, Trogan E, et al. High-density lipoproteins retard the progression of atherosclerosis and favorably remodel lesions without suppressing indices of inflammation or oxidation. Arterioscler Thromb Vasc Biol 2004;24:1904–9.
587
[5] Michel JB. Anoikis in the cardiovascular system: known and unknown extracellular mediators. Arterioscler Thromb Vasc Biol 2003;23:2146–54. [6] Park HK, Park EC, Bae SW, et al. Expression of heat shock protein 27 in human atherosclerotic plaques and increased plasma level of heat shock protein 27 in patients with acute coronary syndrome. Circulation 2006;114:886–93. [7] Hedges JC, Dechert MA, Yamboliev IA, et al. A role for p38(MAPK)/HSP27 pathway in smooth muscle cell migration. J Biol Chem 1999;274:24211–9. [8] Martin-Ventura JL, Duran MC, Blanco-Colio LM, et al. Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of atherosclerosis. Circulation 2004;110:2216–9.
0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2012.09.226
Heme oxygenase-1: An important therapeutic target for protecting against myocardial ischemia and reperfusion injury Xiaorong Hu 1, Jichun Wang 1, Hong Jiang ⁎ Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
a r t i c l e
i n f o
Article history: Received 8 September 2012 Accepted 29 September 2012 Available online 18 October 2012 Keywords: Myocardial ischemia Reperfusion Heme oxygenase-1 Cardioprotectoion
Myocardial reperfusion therapy (such as thrombolysis and percutaneous coronary intervention) is the optimal therapeutic strategy for acute myocardial infarction, which could preserve myocardial viability and function by reversing myocardial ischemia and reducing the infarct size and has been endorsed in clinical practice [1]. However, the subsequent ischemia and reperfusion (I/R) injury may attenuate the therapeutic benefit [1]. Although reperfusion therapy is essential for the survival of ischemic tissue, reperfusion itself could cause additional cellular injury. I/R could cause local myocardial inflammation, accompanying with apoptosis, which could result in myocardial cell damage [2]. High mobility group box 1 protein (HMGB1), a highly conserved nuclear protein that could regulate gene transcription and maintain the nucleosome structure, could be passively released from necrotic cell, apoptotic cell or actively secreted by innate immune cells (such as macrophages and monocytes) [3,4]. Present study shows that HMGB1 functions as a novel pro-inflammatory cytokine and promotes the progress of myocardial I/R injury [5]. HMGB1 could promote the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), whereas HMGB1 A box peptide (a specific HMGB1 antagonist) could reduce myocardial ischemia and reperfusion injury and inhibit the release of TNF-α and IL-6 [5], indicating that inhibiting HMGB1 expression could ⁎ Corresponding author at: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, 430060, China. Tel.: + 86 27 88041911; fax: + 86 27 88040334. E-mail address: [email protected] (H. Jiang). 1 These authors contributed equally to this study as co-first author.
suppress the inflammatory process. Meanwhile, lots of drugs have been found to reduce myocardial I/R injury by inhibiting HMGB1 expression, including asperosaponin X [6], minocycline [7], ethyl pyruvate [8], etc. These suggested that HMGB1 may be a potential therapeutic target for myocardial I/R injury and inhibiting HMGB1 could reduce myocardial I/R injury [9]. Heme oxygenase-1 (HO-1), an inducible isoform of heme oxygenase (HO) enzymes, has been proved that it involves inhibition of early pro-inflammatory cytokines, such as TNF-α and IL-6 which could promote cell apoptosis, and induction of the anti-inflammatory cytokine- (IL-10) which could inhibit cell apoptosis [10,11]. Recently, Liu et al. [12] showed that hydroxysafflor yellow A could provide a protective effect on anoxia/reoxygenation (same as I/R) -induced apoptosis and injury in H9c2 cardiomyocytes and upregulate expression and activity of HO-1, while an HO-1 inhibitor could completely suppress HO-1 enzymatic activity upregulated by hydroxysafflor yellow A and notably diminished the anti-apoptotic effect of hydroxysafflor yellow A, indicating that HO-1 may play an important protective effect on anoxia/reoxygenation or I/R injury. In addition, Takamiya et al. [13] have demonstrated that the circulating levels of HMGB1 were higher in HO-1−/− mice than HO-1+/+ mice and the HO-1−/− mice given HMGB1 neutralizing antibody showed improvement in survival compared with littermates receiving control antibody. In addition, the HO-1 induction has also been shown that it could prevent the release of HMGB1 inendotoxin-activated macrophages in vitro and septic animals in vivo [14]. These results suggested that the HO-1 induction plays an important role in anti-inflammatory effect and could prevent anoxia/reoxygenation or I/R injury by inhibiting HMGB1 release. In conclusion, upregulating HO-1 expression may provide a protective effect on myocardial I/R injury which may be associated with inhibiting HMGB1 expression; HO-1 may be an important therapeutic target for protecting against myocardial I/R injury. This study was partially supported by a grant from the National Natural Science Foundation of China (No. 81100146), grant 111023 from the Fundamental Research Funds for the Central Universities and the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20110141120060). The authors of this manuscript have also certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
588
Letters to the Editor
References [1] Takemura G, Nakagawa M, Kanamori H, et al. Benefits of reperfusion beyond infarction size limitation. Cardiovasc Res 2009;83:269–76. [2] Frangoginis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res 2002;53:31–47. [3] Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002;418:191–5. [4] Bell CW, Jiang W, Reich CF, et al. The extracellular release of HMGB1 during apoptotic cell death. Am J Physiol Cell Physiol 2006;291:C1318–25. [5] Andrassy M, Volz HC, Igwe JC, et al. High-mobility group box-1 in ischemia– reperfusion injury of the heart. Circulation 2008;117:3216–26. [6] Jiang WL, Zhang SP, Zhu HB, et al. Cardioprotection of asperosaponin X on experimental myocardial ischemia injury. Int J Cardiol 2012;155:430–6. [7] Hu X, Zhou X, Xu C, et al. Minocycline protects against myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats. Eur J Pharmacol 2011;654:274–9. [8] Hu X, Cui B, Zhou X, et al. Ethyl pyruvate reduces myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats. Mol Biol Rep 2012;19:227–31.
[9] Hu X, Fu W, Jiang H. HMGB1: a potential therapeutic target for myocardial ischemia and reperfusion injury. Int J Cardiol 2012;155:489-489. [10] Abraham NG, Kappas A. Heme oxygenase and the cardiovascular-renal system. Free Radic Biol Med 2005;39:1–25. [11] Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 2006;86:583–650. [12] Liu SX, Zhang Y, Wang YF, et al. Upregulating of heme oxyenase-1 expression by hydroxysafflor yellow A conferring protection from anoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes. Int J Cardiol 2012;160:95–101. [13] Takamiya R, Hung CC, Hall SR, et al. High-mobility group box 1 contributes to lethality of endotoxemia in heme oxygenase-1-deficient mice. Am J Respir Cell Mol Biol 2009;41:129–35. [14] Tsoyi K, Lee TY, Lee YS, et al. Heme-oxygenase-1 induction and carbon monoxidereleasing molecule inhibit lipopolysaccharide (LPS)-induced high-mobility group box 1 release in vitro and improve survival of mice in LPS- and cecal ligation and punctureinduced sepsis model in vivo. Mol Pharmacol 2009;76:173–82.
0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2012.09.225
Cryoenergy is effective in the treatment of resistant hypertension in non-responders to radiofrequency renal denervation Dirk Prochnau ⁎,1, Hans R. Figulla 1, Ralf Surber 1 Department of Internal Medicine I, Friedrich Schiller University, Jena, Germany
a r t i c l e
i n f o
Article history: Received 7 September 2012 Accepted 29 September 2012 Available online 23 October 2012 Keywords: Resistant hypertension Renal denervation Cryoenergy Non-responders Radiofrequency
in a sheep model [4]. In this animal model, an almost total loss of neurofilaments in the created lesions was observed representing a surrogate marker for effective sympathetic denervation [4]. Here we describe for the first time that cryoablation, as second-line therapy for sympathetic denervation of the renal arteries, is safe and effective in patients with ongoing resistant HTN despite optimized medical treatment and previous unsuccessful RDN with RF current. In this pilot study, three patients with drug resistant hypertension (from a population with a responder rate of 80% [5]) who did not show the intended treatment goal with RF current (reduction of the mean 24h ambulatory BP≥ 10 mm Hg) underwent cryoablation for RDN. One patient with end stage renal disease (ERSD) was successfully treated initially with RF ablation of the renal artery. Twelve months later,
To the Editor, Percutaneous catheter-based renal denervation (RDN) is a new treatment option for drug-resistant hypertension (HTN) [1,2]. Until now, radiofrequency (RF) current is the predominant energy source used for ablation of the renal nerves. However, according to the literature, about 15–20% of treated patients are non-responders to the RDN therapy, indicated by a post-interventional reduction of systolic blood pressure (BP) less than 10 mm Hg [1,2]. In the treatment of cardiac arrhythmias, it was shown that the use of cryoenergy, in comparison to RF current, is accompanied by a reduction of pain and discomfort during ablation without significant differences in the rate of effectiveness [3]. Consequently, this approach might also be used for RDN in drug resistant hypertension to reduce the pain during the procedure, achieve a more effective RDN and minimize the number of non-responders. Recently, we demonstrated that cryoablation of the renal artery is feasible and safe
⁎ Corresponding author at: Department of Internal Medicine I, Friedrich Schiller University, Erlanger Allee 101, 07740 Jena, Germany. Tel.: +49 3641 9324541; fax: +49 3641 9324102. E-mail address: [email protected] (D. Prochnau). 1 All three authors contributed equally to this work.
Table 1 Baseline patient characteristics. Parameter
Patient 1
Patient 2
Patient 3
Sex Age (yr) Time after renal denervation with RF current (months) Comorbidity Diabetes mellitus CAD Chronic renal insufficiency (creatinine N 130 μmol/l) Obstructive sleep apnoea (treated) Body mass index Number of antihypertensive medication Baseline Changes at three-month follow-up 24-h ABPM (mm Hg) Baseline At 1 month At 3 months
Male 38 12
Male 70 4
Male 48 4
− − +
+ + +
− − −
− 18.0
+ 47.5
+ 31.8
6 −3
7 −2
5 No change
189/115 104/63 106/66
154/81 132/73 132/69
187/104 128/88 161/100
Yr, years; RF, radiofrequency; CAD, coronary artery disease; ABPM, ambulatory blood pressure monitoring.