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Immunology of cardiovascular disorders
Immunobiology 217 (2012) 467
Contents lists available at SciVerse ScienceDirect
Immunobiology journal homepage: www.elsevier.de/imbio
Introduction
Immunology of cardiovascular disorders Cardiovascular disorders are the leading cause of mortality in developed societies. Accumulating evidence indicates that unbalanced or autoreactive dispositions of the immune system critically contribute to many forms of cardiovascular disorders. The immune system is not only designed to clear the body of infectious or toxic exogenous challenges but also to guard a homeostatic balance and ensure efficient clearance of unwanted-self substances. In response to pathogen attacks or trauma, the immune system mounts an acute inflammatory reaction to eliminate pathogenic non-self agents, resolve inflammation, and to coordinate healing and repair. However, the fine-tuning of these complex tasks is heavily influenced by genetic, metabolic, life style, and stress factors as well as ageing and imbalanced immune responses, especially if they are perpetuated over longer periods of time, leading to the development of cardiovascular disorders. A persistent pro-inflammatory disposition caused by either the failure to clear pro-inflammatory stimuli or to resolve acute inflammatory responses can result in development of chronic inflammatory conditions and/or fibrosis. Atherosclerosis – for example – is a chronic inflammatory disorder that can develop asymptomatically for decades that in its advanced stages may finally lead up to life-threatening events such as myocardial infarction or stroke. Here, a chronic inflammatory processes within atherosclerotic plaques formed on the wall of major arteries can result in acute plaque rapture initiating formation of a larger thrombus, which can obstruct and block smaller vessels, causing ischaemic pathologies. In case of myocarditis, patients that survive the acute inflammation phase have a good long-term prognosis compared to patients with moderate chronic inflammatory reactions. Fibrotic processes driven by chronic pro-inflammatory events present as additional parameters that contribute to the development of heart failure. Thus, achieving the fine-balance between an effective acute inflammatory response that resolves and initiates healing processes has to be considered as the primary aim of immunomodulatory therapies in the treatment of cardiovascular disorders. The current Special Issue highlights clinically relevant issues in pathophysiology of life threatening cardiovascular disorders including atherosclerosis, viral myocarditis, and dilated cardiomyopathy. We aim to emphasise and highlight the limitation of presently applied diagnostic and therapeutic approaches. Multiple human and animal cell-based experiential in vitro models and animal disease models for atherosclerosis and myocarditis provided comprehensive knowledge about pathways, cell types and molecules that are critical for the development of cardiovascular pathologies. Recent advances in the understanding of the immune cellular activation, their interaction with extracellular matrix, function of their receptors, intracellular pathways, and released factors in the pathogenesis of cardiovascular disorders are presented in the current issue. Special attention is given to the diversity and 0171-2985/$ – see front matter © 2012 Elsevier GmbH. All rights reserved. doi:10.1016/j.imbio.2012.02.012
plasticity of monocyte-derived macrophages, and a recently discovered mechanism of cooperation between scavenger receptors and Toll-like receptors inducing inflammation in atherosclerosis. Eminent contributors to this Special Issue present the cutting edge of our current understanding of the pathophysiological processes leading up to dilated cardiomyopathy and highlight how the crosstalk between innate and adaptive immunity links viral infection of myocardium to the development of auto-antibodies to beta1adrenoreceptors expressed on cardiomyocytes. This Special Issue emphasises the need to develop novel therapeutic concepts to block disease-promoting immune processes including the increased infiltration of monocytes in atherosclerotic plaques, or the binding of modified lipoproteins to scavenger receptors, or the extraction of circulating auto-antibodies to beta1adrenoreceptors by immunoadsorption. We also highlight the need for the development of innovative, sensitive and affordable diagnostic approaches. As such, the phenotype of circulating monocytes or measurement of concentration of macrophage-released soluble and matrix factors could be predictive even at early stages of cardiovascular disorders, long before they manifest clinically and use the immune system to sense pathophysiological events. Novel biomarkers, such as stabilin-1 and other scavenger receptors expressed on the surface of circulating monocytes in pre-atherosclerotic conditions or elevated levels of chitinase-like protein YKL-40 in ischaemic heart disease require further validation on large cohorts of patients. Combining mechanistic findings made in the experimental systems with evaluation of biomarkers of pathological reactions of innate and adaptive immune systems using large cohorts of patients with various genetic backgrounds will make it possible to achieve the aims of predictive, preventive and personalised medicine. Julia Kzhyshkowska ∗ Medical Faculty Mannheim, University of Heidelberg, Germany Wilhelm Schwaeble Department of Infection, Immunity and Inflammation, University of Leicester, UK Siamon Gordon Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK ∗ Corresponding
author. Tel.: +49 6213832440; fax: +49 6213833815. E-mail address: [email protected] (J. Kzhyshkowska) 19 February 2012
Contents lists available at SciVerse ScienceDirect
Immunobiology journal homepage: www.elsevier.de/imbio
Introduction
Immunology of cardiovascular disorders Cardiovascular disorders are the leading cause of mortality in developed societies. Accumulating evidence indicates that unbalanced or autoreactive dispositions of the immune system critically contribute to many forms of cardiovascular disorders. The immune system is not only designed to clear the body of infectious or toxic exogenous challenges but also to guard a homeostatic balance and ensure efficient clearance of unwanted-self substances. In response to pathogen attacks or trauma, the immune system mounts an acute inflammatory reaction to eliminate pathogenic non-self agents, resolve inflammation, and to coordinate healing and repair. However, the fine-tuning of these complex tasks is heavily influenced by genetic, metabolic, life style, and stress factors as well as ageing and imbalanced immune responses, especially if they are perpetuated over longer periods of time, leading to the development of cardiovascular disorders. A persistent pro-inflammatory disposition caused by either the failure to clear pro-inflammatory stimuli or to resolve acute inflammatory responses can result in development of chronic inflammatory conditions and/or fibrosis. Atherosclerosis – for example – is a chronic inflammatory disorder that can develop asymptomatically for decades that in its advanced stages may finally lead up to life-threatening events such as myocardial infarction or stroke. Here, a chronic inflammatory processes within atherosclerotic plaques formed on the wall of major arteries can result in acute plaque rapture initiating formation of a larger thrombus, which can obstruct and block smaller vessels, causing ischaemic pathologies. In case of myocarditis, patients that survive the acute inflammation phase have a good long-term prognosis compared to patients with moderate chronic inflammatory reactions. Fibrotic processes driven by chronic pro-inflammatory events present as additional parameters that contribute to the development of heart failure. Thus, achieving the fine-balance between an effective acute inflammatory response that resolves and initiates healing processes has to be considered as the primary aim of immunomodulatory therapies in the treatment of cardiovascular disorders. The current Special Issue highlights clinically relevant issues in pathophysiology of life threatening cardiovascular disorders including atherosclerosis, viral myocarditis, and dilated cardiomyopathy. We aim to emphasise and highlight the limitation of presently applied diagnostic and therapeutic approaches. Multiple human and animal cell-based experiential in vitro models and animal disease models for atherosclerosis and myocarditis provided comprehensive knowledge about pathways, cell types and molecules that are critical for the development of cardiovascular pathologies. Recent advances in the understanding of the immune cellular activation, their interaction with extracellular matrix, function of their receptors, intracellular pathways, and released factors in the pathogenesis of cardiovascular disorders are presented in the current issue. Special attention is given to the diversity and 0171-2985/$ – see front matter © 2012 Elsevier GmbH. All rights reserved. doi:10.1016/j.imbio.2012.02.012
plasticity of monocyte-derived macrophages, and a recently discovered mechanism of cooperation between scavenger receptors and Toll-like receptors inducing inflammation in atherosclerosis. Eminent contributors to this Special Issue present the cutting edge of our current understanding of the pathophysiological processes leading up to dilated cardiomyopathy and highlight how the crosstalk between innate and adaptive immunity links viral infection of myocardium to the development of auto-antibodies to beta1adrenoreceptors expressed on cardiomyocytes. This Special Issue emphasises the need to develop novel therapeutic concepts to block disease-promoting immune processes including the increased infiltration of monocytes in atherosclerotic plaques, or the binding of modified lipoproteins to scavenger receptors, or the extraction of circulating auto-antibodies to beta1adrenoreceptors by immunoadsorption. We also highlight the need for the development of innovative, sensitive and affordable diagnostic approaches. As such, the phenotype of circulating monocytes or measurement of concentration of macrophage-released soluble and matrix factors could be predictive even at early stages of cardiovascular disorders, long before they manifest clinically and use the immune system to sense pathophysiological events. Novel biomarkers, such as stabilin-1 and other scavenger receptors expressed on the surface of circulating monocytes in pre-atherosclerotic conditions or elevated levels of chitinase-like protein YKL-40 in ischaemic heart disease require further validation on large cohorts of patients. Combining mechanistic findings made in the experimental systems with evaluation of biomarkers of pathological reactions of innate and adaptive immune systems using large cohorts of patients with various genetic backgrounds will make it possible to achieve the aims of predictive, preventive and personalised medicine. Julia Kzhyshkowska ∗ Medical Faculty Mannheim, University of Heidelberg, Germany Wilhelm Schwaeble Department of Infection, Immunity and Inflammation, University of Leicester, UK Siamon Gordon Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK ∗ Corresponding
author. Tel.: +49 6213832440; fax: +49 6213833815. E-mail address: [email protected] (J. Kzhyshkowska) 19 February 2012