1. The failing heart stimulates tumor growth by circulating factors
- Author
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Meijers, WC, Maglione, M, Bakker, SJL, Oberhuber, R, Kieneker, LM, De Jong, S, Haubner, BJ, Nagengast, WB, Lyon, AR, Van der Vegt, B, Van Veldhuisen, DJ, Westenbrink, BD, Van der Meer, P, Silljé, HHW, De Boer, RA, and British Heart Foundation more...
- Subjects
Science & Technology ,Cardiac & Cardiovascular Systems ,myocardial infarction ,proteomics ,Cardiovascular System & Hematology ,Cardiovascular System & Cardiology ,biomarkers ,cancer ,heart failure ,Life Sciences & Biomedicine ,1102 Cardiovascular Medicine And Haematology - Abstract
Background—Heart failure (HF) survival has improved and nowadays many patients with HF die from non-cardiac 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 (MI) in APCmin mice, which are prone to develop precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was employed, where 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-MI 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 HF patients. 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 2.4fold in APCmin mice (all P more...
- Published
- 2018