International Journal of Cardiology 177 (2014) 142–143
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Acute myocardial infarction and mortality in patients with systemic lupus erythematosus: The role of inflammatory cells and of Kounis syndrome George N. Kounis a, George D. Soufras b, Nicholas G. Kounis c,⁎ a b c
Department of General Medicine, University of Patras Medical School, Patras, Achaia, Greece Department of Cardiology, “Saint Andrews” State General Hospital, Patras, Achaia, Greece Department of Medical Sciences, Southwestern Greece Highest Institute of Education and Technology Patras, Greece
a r t i c l e
i n f o
Article history: Received 30 August 2014 Accepted 17 September 2014 Available online 28 September 2014 Keywords: Acute myocardial infarction Inflammation Kounis syndrome Systemic lupus erythematosus
In the interesting retrospective study published in Int J Cardiol [1] the authors concluded that patients with systemic lupus erythematosus had higher risk of acute myocardial infarction compared to control healthy group. Furthermore, this risk was more significant in females and systemic lupus erythematosus was an independent risk factor for mortality following acute myocardial infarction. Although, they speculated on persistent systemic vascular inflammation, corticosteroid treatment causing hypertension, renal problems such as nephritis and proatherogenic or prothrombotic risk factors such as dyslipidemia and antiphospholipid antibodies, they did not elaborate on the pathopysiologic mechanisms associated with this disease. Systemic lupus erythematosus is an autoimmune inflammatory disease of unknown origin that affects all the organ systems. Chronic inflammation associated with systemic lupus erythematosus can induce abnormal vasomotion by reduction of NO production and increase of endothelin-1 release leading to coronary artery spasm which can progress to acute myocardial infarction as a result of endothelial injury and damage. This could be the result of either increase of CRP which induces significant expression of endothelial damaging molecules such as ICAM-1, VCAM-1 and e-selectin or expansion of ⁎ Corresponding author at: Queen Olgas Square, 7 Aratou Street, Patras 26221, Greece. Tel./fax: +30 2610 279579. E-mail address: [email protected] (N.G. Kounis).
http://dx.doi.org/10.1016/j.ijcard.2014.09.070 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
CD4 CD28 T cells which induce cytolytic effects on endothelial cells and/or activation of macrophages [2]. This autoimmune disease is associated with all types of inflammatory cells that drive to the development of coronary events and arterial thrombosis. Apart from genetic and environmental factors, autoantibody and immune complex deposition as well as cytokine imbalances contribute to immune dysfunction. Interleukin-9, that is a T cellderived factor preferentially expressed by CD4+ T cells and has been characterized in human and murine systems, has been found increased in systemic lupus erythematosus [3]. Mast cell tryptase that can be an indicator of type I hypersensitivity reaction and may serve as a surrogate marker of anaphylaxis is raised in systemic lupus erythematosus [4]. An association between hypereosinophilic syndrome and systemic lupus erythematosus has been also reported [5]. Furthermore, the presence of macrophages and their polarization has been found to contribute to the initiation and perpetuation of systemic lupus erythematosus [6]. We have found that all these inflammatory cells, namely T-cells, macrophages together with eosinophils and mast cells participate in a vicious inflammatory cycle behaving as a “ball of thread” and via multidirectional signals activate each other for example: T cells can mediate mast cell activation and proliferation, mast cells can enhance T cell activation, inducible macrophage protein-1α can activate mast cells, mast cells can activate macrophages and T cells can regulate macrophage activity [7]. Eosinophils express H4 histamine receptors which facilitate eosinophil chemotaxis toward mast cells which are the major producers of inflammatory mediators. Mast cell secreted mediators and eosinophils modulate also reciprocal interactions between these two cells in the so called “allergic effector unit” [8]. These two types of cells are important effector cells in the late phase allergic response and they have been implicated in both pathogenesis of inflammatory hypersensitivity diseases and acute coronary events [9]. However, in lupus erythematosus and other autoimmune conditions, including rheumatoid arthritis, mast cells, macrophages and few eosinophils are present in inflamed rheumatoid synovial tissue and sites of cartilage. Such findings are at variance with those in allergic inflammation, in which the presence of eosinophils has been reported to be regulated by specific chemokines and adhesion molecules [9]. Therefore an association with Kounis syndrome [10] cannot be excluded. Consequently, in order to elucidate the pathophysiology and to discover potential therapeutic and preventing measures for acute coronary events, searching
G.N. Kounis et al. / International Journal of Cardiology 177 (2014) 142–143
for inflammatory cells and measurement of inflammatory cell mediators released from these cells should be always performed. In the paper of Lin et al. [1] some patients with systemic lupus erythematosus have had cardiac surgeries, and it was found that their 30-day in-hospital mortality was significantly higher compared to non-diseased patients. This was attributed to active inflammatory status, corticosteroids or immunosuppressant treatments, and progressive organ damage. This group of patients could have been an ideal cohort for hematologic and histochemical searching for inflammatory cells and their inflammatory mediators.
[2]
[3] [4] [5]
[6]
Conflict of interest
[7]
The authors report no relationships that could be construed as a conflict of interest.
[8] [9]
References [1] Lina Chiao-Yi, Shihb Chun-Chuan, Yehc Chun-Chieh, Choud Wan-Hsin, Chend Ta-Liang, Liao Chien-Chang. Increased risk of acute myocardial infarction and mortality in patients with systemic lupus erythematosus: two nationwide
[10]
143
retrospective cohort studies. Int J Cardiol 2014. http://dx.doi.org/10.1016/j. ijcard.2014.08.006. Ong P, Athanasiadis A, Alscher MD, et al. Coronary artery spasm as a cause for myocardial infarction in patients with systemic inflammatory disease. Int J Cardiol 2011;151:e32–4. Ouyang H, Shi Y, Liu Z, et al. Increased interleukin 9 and CD4 + IL-9+ T cells in patients with systemic lupus erythematosus. Mol Med Rep 2013;7:1031–7. Carson HJ, Cook BA. Mast cell tryptase in a case of anaphylaxis due to repeat antibiotic exposure. Leg Med (Tokyo) 2009;11:234–6. Habibagahi Z, Ali Nazarinia M, Aaflaki E, Ali Ostovan M, Hadi Bagheri M. Systemic lupus erythematosus and hyper-eosinophilic syndrome: an unusual association. West Indian Med J 2009;58:69–71. Xiao P, Dong C, Yue Y, Xiong S. Dynamic expression of microRNAs in M2b polarized macrophages associated with systemic lupus erythematosus. Gene. 2014; 547: 300–309. Almpanis G, Mazarakis A, Tsigkas G, Koutsojannis C, Kounis GN, Kounis NG. Acute stent thrombosis and atopy: implications for Kounis syndrome. Int J Cardiol 2010; 145:398–400. Kounis NG. Eosinophils and Kounis hypersensitivity associated syndrome as contributors to very late coronary stent thrombosis. Int J Cardiol 2013;167:594–5. Almpanis GC, Kounis GN, Mazarakis A, Kounis NG. Coronary artery spasm progressing to acute myocardial infarction in patients with systemic inflammatory disease: a potential association with Kounis syndrome. Int J Cardiol 2011;151:1–2. Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol 2006;110:7–14.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Acute myocardial infarction and mortality in patients with systemic lupus erythematosus: The role of inflammatory cells and of Kounis syndrome George N. Kounis a, George D. Soufras b, Nicholas G. Kounis c,⁎ a b c
Department of General Medicine, University of Patras Medical School, Patras, Achaia, Greece Department of Cardiology, “Saint Andrews” State General Hospital, Patras, Achaia, Greece Department of Medical Sciences, Southwestern Greece Highest Institute of Education and Technology Patras, Greece
a r t i c l e
i n f o
Article history: Received 30 August 2014 Accepted 17 September 2014 Available online 28 September 2014 Keywords: Acute myocardial infarction Inflammation Kounis syndrome Systemic lupus erythematosus
In the interesting retrospective study published in Int J Cardiol [1] the authors concluded that patients with systemic lupus erythematosus had higher risk of acute myocardial infarction compared to control healthy group. Furthermore, this risk was more significant in females and systemic lupus erythematosus was an independent risk factor for mortality following acute myocardial infarction. Although, they speculated on persistent systemic vascular inflammation, corticosteroid treatment causing hypertension, renal problems such as nephritis and proatherogenic or prothrombotic risk factors such as dyslipidemia and antiphospholipid antibodies, they did not elaborate on the pathopysiologic mechanisms associated with this disease. Systemic lupus erythematosus is an autoimmune inflammatory disease of unknown origin that affects all the organ systems. Chronic inflammation associated with systemic lupus erythematosus can induce abnormal vasomotion by reduction of NO production and increase of endothelin-1 release leading to coronary artery spasm which can progress to acute myocardial infarction as a result of endothelial injury and damage. This could be the result of either increase of CRP which induces significant expression of endothelial damaging molecules such as ICAM-1, VCAM-1 and e-selectin or expansion of ⁎ Corresponding author at: Queen Olgas Square, 7 Aratou Street, Patras 26221, Greece. Tel./fax: +30 2610 279579. E-mail address: [email protected] (N.G. Kounis).
http://dx.doi.org/10.1016/j.ijcard.2014.09.070 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
CD4 CD28 T cells which induce cytolytic effects on endothelial cells and/or activation of macrophages [2]. This autoimmune disease is associated with all types of inflammatory cells that drive to the development of coronary events and arterial thrombosis. Apart from genetic and environmental factors, autoantibody and immune complex deposition as well as cytokine imbalances contribute to immune dysfunction. Interleukin-9, that is a T cellderived factor preferentially expressed by CD4+ T cells and has been characterized in human and murine systems, has been found increased in systemic lupus erythematosus [3]. Mast cell tryptase that can be an indicator of type I hypersensitivity reaction and may serve as a surrogate marker of anaphylaxis is raised in systemic lupus erythematosus [4]. An association between hypereosinophilic syndrome and systemic lupus erythematosus has been also reported [5]. Furthermore, the presence of macrophages and their polarization has been found to contribute to the initiation and perpetuation of systemic lupus erythematosus [6]. We have found that all these inflammatory cells, namely T-cells, macrophages together with eosinophils and mast cells participate in a vicious inflammatory cycle behaving as a “ball of thread” and via multidirectional signals activate each other for example: T cells can mediate mast cell activation and proliferation, mast cells can enhance T cell activation, inducible macrophage protein-1α can activate mast cells, mast cells can activate macrophages and T cells can regulate macrophage activity [7]. Eosinophils express H4 histamine receptors which facilitate eosinophil chemotaxis toward mast cells which are the major producers of inflammatory mediators. Mast cell secreted mediators and eosinophils modulate also reciprocal interactions between these two cells in the so called “allergic effector unit” [8]. These two types of cells are important effector cells in the late phase allergic response and they have been implicated in both pathogenesis of inflammatory hypersensitivity diseases and acute coronary events [9]. However, in lupus erythematosus and other autoimmune conditions, including rheumatoid arthritis, mast cells, macrophages and few eosinophils are present in inflamed rheumatoid synovial tissue and sites of cartilage. Such findings are at variance with those in allergic inflammation, in which the presence of eosinophils has been reported to be regulated by specific chemokines and adhesion molecules [9]. Therefore an association with Kounis syndrome [10] cannot be excluded. Consequently, in order to elucidate the pathophysiology and to discover potential therapeutic and preventing measures for acute coronary events, searching
G.N. Kounis et al. / International Journal of Cardiology 177 (2014) 142–143
for inflammatory cells and measurement of inflammatory cell mediators released from these cells should be always performed. In the paper of Lin et al. [1] some patients with systemic lupus erythematosus have had cardiac surgeries, and it was found that their 30-day in-hospital mortality was significantly higher compared to non-diseased patients. This was attributed to active inflammatory status, corticosteroids or immunosuppressant treatments, and progressive organ damage. This group of patients could have been an ideal cohort for hematologic and histochemical searching for inflammatory cells and their inflammatory mediators.
[2]
[3] [4] [5]
[6]
Conflict of interest
[7]
The authors report no relationships that could be construed as a conflict of interest.
[8] [9]
References [1] Lina Chiao-Yi, Shihb Chun-Chuan, Yehc Chun-Chieh, Choud Wan-Hsin, Chend Ta-Liang, Liao Chien-Chang. Increased risk of acute myocardial infarction and mortality in patients with systemic lupus erythematosus: two nationwide
[10]
143
retrospective cohort studies. Int J Cardiol 2014. http://dx.doi.org/10.1016/j. ijcard.2014.08.006. Ong P, Athanasiadis A, Alscher MD, et al. Coronary artery spasm as a cause for myocardial infarction in patients with systemic inflammatory disease. Int J Cardiol 2011;151:e32–4. Ouyang H, Shi Y, Liu Z, et al. Increased interleukin 9 and CD4 + IL-9+ T cells in patients with systemic lupus erythematosus. Mol Med Rep 2013;7:1031–7. Carson HJ, Cook BA. Mast cell tryptase in a case of anaphylaxis due to repeat antibiotic exposure. Leg Med (Tokyo) 2009;11:234–6. Habibagahi Z, Ali Nazarinia M, Aaflaki E, Ali Ostovan M, Hadi Bagheri M. Systemic lupus erythematosus and hyper-eosinophilic syndrome: an unusual association. West Indian Med J 2009;58:69–71. Xiao P, Dong C, Yue Y, Xiong S. Dynamic expression of microRNAs in M2b polarized macrophages associated with systemic lupus erythematosus. Gene. 2014; 547: 300–309. Almpanis G, Mazarakis A, Tsigkas G, Koutsojannis C, Kounis GN, Kounis NG. Acute stent thrombosis and atopy: implications for Kounis syndrome. Int J Cardiol 2010; 145:398–400. Kounis NG. Eosinophils and Kounis hypersensitivity associated syndrome as contributors to very late coronary stent thrombosis. Int J Cardiol 2013;167:594–5. Almpanis GC, Kounis GN, Mazarakis A, Kounis NG. Coronary artery spasm progressing to acute myocardial infarction in patients with systemic inflammatory disease: a potential association with Kounis syndrome. Int J Cardiol 2011;151:1–2. Kounis NG. Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm? Int J Cardiol 2006;110:7–14.
