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Heart Failure Stimulates Tumor Growth by Circulating Factors

Meijers, W. C., Maglione, M., Bakker, S. J. L., Oberhuber, R., Kieneker, L. M., de Jong, S., Haubner, B. J., Nagengast, W. B., Lyon, A. R., van der Vegt, B., van Veldhuisen, D. J., Westenbrink, B. D., van der Meer, P., Silljé, H. H. W. & de Boer, R. A., 14-Aug-2018, In : Circulation. 138, 7, p. 678-691 14 p.

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  • Heart Failure Stimulates Tumor Growth by Circulating Factors

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Background: Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer.

Methods: HF was induced by inflicting large anterior myocardial infarction in APC(min) mice, which are prone to developing precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was used in which an infarcted or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post-myocardial infarction proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and patients with HF. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large, prospective general population cohort.

Results: The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4-fold in APC(min) mice (all P

Conclusions: We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.

Original languageEnglish
Pages (from-to)678-691
Number of pages14
JournalCirculation
Volume138
Issue number7
Publication statusPublished - 14-Aug-2018

    Keywords

  • biomarkers, heart failure, myocardial infarction, neoplasms, proteomics, PRESERVED EJECTION FRACTION, COLORECTAL-CANCER, TAKOTSUBO CARDIOMYOPATHY, CARDIOVASCULAR TOXICITY, INCREASED RISK, MORTALITY, POPULATION, BIOMARKERS, CELLS, CERULOPLASMIN

ID: 54602087