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      Cardiac cachexia: hic et nunc.

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          Abstract

          Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF.

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          Most cited references169

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          ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

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            Cancer cachexia: mediators, signaling, and metabolic pathways.

            Cancer cachexia is characterized by a significant reduction in body weight resulting predominantly from loss of adipose tissue and skeletal muscle. Cachexia causes reduced cancer treatment tolerance and reduced quality and length of life, and remains an unmet medical need. Therapeutic progress has been impeded, in part, by the marked heterogeneity of mediators, signaling, and metabolic pathways both within and between model systems and the clinical syndrome. Recent progress in understanding conserved, molecular mechanisms of skeletal muscle atrophy/hypertrophy has provided a downstream platform for circumventing the variations and redundancy in upstream mediators and may ultimately translate into new targeted therapies. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival.

              Muscle wasting and cachexia have long been postulated to be key determinants of cancer-related death, but there has been no direct experimental evidence to substantiate this hypothesis. Here, we show that in several cancer cachexia models, pharmacological blockade of ActRIIB pathway not only prevents further muscle wasting but also completely reverses prior loss of skeletal muscle and cancer-induced cardiac atrophy. This treatment dramatically prolongs survival, even of animals in which tumor growth is not inhibited and fat loss and production of proinflammatory cytokines are not reduced. ActRIIB pathway blockade abolished the activation of the ubiquitin-proteasome system and the induction of atrophy-specific ubiquitin ligases in muscles and also markedly stimulated muscle stem cell growth. These findings establish a crucial link between activation of the ActRIIB pathway and the development of cancer cachexia. Thus ActRIIB antagonism is a promising new approach for treating cancer cachexia, whose inhibition per se prolongs survival. Copyright 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                J Cachexia Sarcopenia Muscle
                Journal of cachexia, sarcopenia and muscle
                Wiley-Blackwell
                2190-5991
                2190-5991
                Jun 2016
                : 7
                : 3
                Affiliations
                [1 ] Department of CardiologyClinical Hospital ZvezdaraBelgradeSerbia; School of MedicineUniversity of BelgradeBelgradeSerbia.
                [2 ] Innovative Clinical Trials, Department of Cardiology and Pneumology University Medical Center Göttingen (UMG) Göttingen Germany.
                [3 ] Department of Cardiology Charité - Universitätsmedizin Berlin Germany.
                [4 ] Center for Stroke Research Berlin Charité Universitätsmedizin Berlin Germany.
                [5 ] Department of Cardiology and Department of Research and EducationGeneral Hospital CeljeCeljeSlovenia; Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia.
                Article
                JCSM12118
                10.1002/jcsm.12118
                4929818
                27386168
                2ddf02c1-4b6c-4edb-ab48-374708f4e107
                History

                Cachexia,Diagnosis,Heart failure,Prevalence,Treatment
                Cachexia, Diagnosis, Heart failure, Prevalence, Treatment

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