Our mission is to become a worldwide reference for education in the field for all professionals involved in the process to dissemintate knowledge & skills of Acute Cardiovascular Care
Our mission is to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular imaging in Europe.
Our mission: To promote excellence in research, practice, education and policy in cardiovascular health, primary and secondary prevention.
Our goal is to reduce the burden in cardiovascular disease in Europe through percutaneous cardiovascular interventions.
Our Mission is "to improve the quality of life of the population by reducing the impact of cardiac rhythm disturbances and reduce sudden cardiac death"
To improve quality of life and logevity, through better prevention, diagnosis and treatment of heart failure, including the establishment of networks for its management, education and research.
Working Groups goals is to stimulate and disseminate scientific knowledge in different fields of cardiology.
ESC Councils goal is to share knowledge among medical professionals practising in specific cardiology domains.
OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Dr. Lars Gullestad,
Heart failure (HF) is a complex multi-step disorder in which a number of physiological systems participate acting on the myocyte and interstitial cells. The key pathological process that leads to chronic heart failure is cardiac remodeling in response to different stressors. The involvement of neurohormones in the progression of HF has been firmly established leading to new treatment modalities such as angiotensin converting enzyme (ACE) inhibitors, β-blockers and aldosterone antagonists. However, despite state-of-the-art cardiovascular treatment, chronic HF and remodeling continue, suggesting that important pathogenic mechanisms remain unmodified by the present treatment modalities. Different molecular and cellular pathways that are involved in the remodeling process were discussed in the present session. B Schroen (Maastricht, NL) discussed the role of microRNA in her talk “Macrophage-derived microRNA are implicated in heart failure”. Micro RNA are short, non-coding RNAs that inhibit translation or promote degradation of target mRNA and thereby regulate gene expression. Thus they have a key role in the pathogenesis of remodeling through their ability to negatively regulate expression levels of genes involved in both adaptive and maladaptive remodeling. Inflammation plays a role in the pathophysiology of many cardiac diseases including myocarditis, acute myocardial infarction, ventricular remodeling and heart failure. Important questions, however, have been: 1) to what extent and 2) by what mechanisms inflammatory signaling can contribute to the development of heart failure. B Schroens and her group have addressed this question by looking at a key inflammatory microRNA, miR-155. MiR-155 knock out animals shows increased levels of suppressor of cytokine signalling (SOCS)-1 in machrophages, which leads to decreased IL-6 production and thereby reduced hypertrophy. Thus, it appears that miR-155 regulates inflammatory signaling and pro-hypertrophic cytokine release by targeting SOCS1 in macrophages. This suggests that miR-155 could be a target in different cardiovascular diseases, and phase II clinical trials have been started. E Hirsch (Turin, IT) in his talk “PI3K regulation of cardiac remodeling: an inflammatory matter” discussed the role of the signal transduction enzyme phosphoinositide 3-kinase (PI3K) in the remodeling process. PI3Kγ seems to be involved in lecocyte recruitment as well as regulation in the cardiomyocytes. PI3Kγ regulates leukocyte migration by triggering the accumulation of phosphatidyl (3,4,5)-triphosphate at the leading edge, and thus has a prominent role in driving leukocyte chemotaxis and recruitment in sites of inflammation. Leucocyte infiltration seems to be involved in the fibrotic process in the heart, and experimental models in mice expressing a catalytically inactive PI3Kγ shows that these mice are protected from maladaptive remodeling and cardiac dysfunction up to 16 weeks after aortic banding. PI3Kγ has also a function in the cardiomyocytes, as its catalytic activity is critically involved in signaling events controlling ventricular contractility and remodeling in response to mechanical stress. For instance, it regulates β-adrenergic receptor signaling by modulating receptor internalization, a molecular hallmark of heart failure. Again mice with inactive PI3Kγ had preserved systolic function after aortic banding and adaptive hypertrophy developed. Thus PI3Kγ inhibition, through its combined effects in different cell types on leucocyte recruitment and effect on cardiomyocytes, represents a potential tool in the prevention of heart failure. D Hilfiker-Kleiner (Hannover, DE) discussed the role of gp130 in cardiac inflammation and rupture “Cardiac inflammation and rupture: the role of glycoprotein 130”. Inflammatory processes may be involved in the pathogenesis of heart failure (HF), both in clinical and experimental settings. Interleukin (IL)-6 related cytokines such as IL-6, leukemia inhibitory factor (LIF) and cardiotrophin-1, use glycoprotein (gp) 130 as a common signal transducer. The two major signaling cascades activated by the gp130 receptor, SHP2/ERK and STAT pathways, and have been demonstrated to play important roles in cardiac development potentially by regulating cardiomyogenesis, cardiomyocyte survival and growth. In the adult heart, gp130 is involved in hypertrophy, protection and remodeling in response to physiological and pathophysiological stimuli. Experimental studies in animals have clearly shown the protective effects of the gp130/STAT3 system as animal deficient in this signaling cascade shows increased rate of heart failure, ventricular rupture and deaths following myocarddail infarction compared with wild type mice. On the other hand, it has been reported that elevated serum levels of IL-6 cytokines and gp130 proteins are strong prognostic markers for morbidity and mortality in patients with heart failure or after myocardial infarction. The critical question is therefore if this system should be a target for therapeutic intervention after a myocardial infarction in order to prevent the remodeling process. Perhaps patients with chronic heart failure and evidence of increased activity could be a more natural target. Thus, a balanced gp130 signaling appears to be cardioprotective, whereas imbalanced gp130 signaling contributes more to maladaption and heart failure. AM Shah (London, GB) in his talk “Implication of ROS in cardiac inflammation, hypertrophy and fibrosis” discussed the role of reactive oxygen species (ROS) in the remodeling process. Recent year processes in the extracellular matrix have become of interest. Increased fibrosis is a regular feature in heart failure and contributes to diastolic abnormalities with the clinical picture of heart failure with preserved ejection fraction (HFpEF) and arrhythmias. Reactive oxygen species (ROS) has been demonstrated to be involved in the fibrotic process, and the enzyme NOX2 is known to generate ROS. In different animal models Dr Shah demonstrated the link between inflammation and fibrosis that is independent of a hypertrophic response. For instance, in animal experiments angiotensin II infusion increases NOX2 which increases recruitment of leucocytes in the myocardium. This then leads to enhanced fibrosis and a stiffer and less compliant heart. Similar results have been obtained in transgenic mice overexpressing the enzyme. Thus, NOX 2 could be a potential target for therapy being a specific source of ROS rather than non-specific antioxydants that have failed in heart failure clinical trials. Heart failure is a chronic progressive disease where inflammation clearly is involved in the ongoing remodeling process. Although anticytokine therapy so far has been unsuccessful in heart failure, a clearer understanding of basic mechanism and the interplay between the immune system and the heart is a requisite for a more complete understanding of the pathophysiological process and the possibility of novel treatments. The lectures in this session have clearly demonstrated the complex mechanism for the remodeling process and possibly new treatment targets. Further understanding of the molecular mechanism leading to pathological cardiac remodeling is critical for the development of novel therapies aimed at ameliorating cardiac dysfunction
Inflammation as a modulator of cardiac remodelling