Prevention of liver cancer cachexia-induced cardiac wasting and heart failure
Open Access
- 29 August 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in European Heart Journal
- Vol. 35 (14), 932-941
- https://doi.org/10.1093/eurheartj/eht302
Abstract
Symptoms of cancer cachexia (CC) include fatigue, shortness of breath, and impaired exercise capacity, which are also hallmark symptoms of heart failure (HF). Herein, we evaluate the effects of drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development of cardiac wasting, HF, and death in the rat hepatoma CC model (AH-130). Tumour-bearing rats showed a progressive loss of body weight and left-ventricular (LV) mass that was associated with a progressive deterioration in cardiac function. Strikingly, bisoprolol and spironolactone significantly reduced wasting of LV mass, attenuated cardiac dysfunction, and improved survival. In contrast, imidapril had no beneficial effect. Several key anabolic and catabolic pathways were dysregulated in the cachectic hearts and, in addition, we found enhanced fibrosis that was corrected by treatment with spironolactone. Finally, we found cardiac wasting and fibrotic remodelling in patients who died as a result of CC. In living cancer patients, with and without cachexia, serum levels of brain natriuretic peptide and aldosterone were elevated. Systemic effects of tumours lead not only to CC but also to cardiac wasting, associated with LV-dysfunction, fibrotic remodelling, and increased mortality. These adverse effects of the tumour on the heart and on survival can be mitigated by treatment with either the β-blocker bisoprolol or the aldosterone antagonist spironolactone. We suggest that clinical trials employing these agents be considered to attempt to limit this devastating complication of cancer.Keywords
This publication has 36 references indexed in Scilit:
- NF-κB Directly Regulates Fas Transcription to Modulate Fas-mediated Apoptosis and Tumor SuppressionPublished by Elsevier BV ,2012
- Oral Resveratrol Therapy Inhibits Cancer-Induced Skeletal Muscle and Cardiac Atrophy In VivoNutrition and Cancer, 2011
- Increased Proteolysis, Myosin Depletion, and Atrophic AKT-FOXO Signaling in Human Diaphragm DisuseAmerican Journal of Respiratory and Critical Care Medicine, 2011
- Cachexia as a major underestimated and unmet medical need: facts and numbersJournal of Cachexia, Sarcopenia and Muscle, 2010
- Reversal of Cancer Cachexia and Muscle Wasting by ActRIIB Antagonism Leads to Prolonged SurvivalCell, 2010
- Genetic Deletion of Myostatin From the Heart Prevents Skeletal Muscle Atrophy in Heart FailureCirculation, 2010
- Role for precursor Pro-B type natriuretic peptide in assessing response to therapy and prognosis in patients with decompensated heart failure treated with nesiritideClinica Chimica Acta; International Journal of Clinical Chemistry, 2009
- The AP-1/NF-kappaB double inhibitor SP100030 can revert muscle wasting during experimental cancer cachexia.2007
- Relevance of matrix metalloproteinases and their inhibitors after myocardial infarction: A temporal and spatial windowCardiovascular Research, 2006
- Mineralocorticoid Receptor Antagonism Ameliorates Left Ventricular Diastolic Dysfunction and Myocardial Fibrosis in Mildly Symptomatic Patients With Idiopathic Dilated CardiomyopathyCirculation, 2005