Why the study?
To understand the underlying mechanisms of cardiac dysfunction in cancer.
Absolute Event Rate: 46.56% vs 63.4%
p-value: p=<0.0001
In a mouse model, lung tumor cells induced heart failure characterized by impaired cardiac performance, reduced protein synthesis, and altered mitochondrial function.
Lung tumor cells may impair cardiac function via mitochondrial and translational changes in mice; leaves open relevance to human cardio-oncology.
BACKGROUND: To understand the underlying mechanisms of cardiac dysfunction in cancer, we examined cardiac function, protein synthesis, mitochondrial function and gene expression in a model of heart failure in mice injected with Lewis lung carcinoma (LLC1) cells. EXPERIMENTAL DESIGN: Seven week-old C57BL/J6 male and female mice were injected with LLC1 cells or vehicle. Cardiac ejection fraction, ventricular wall and septal thickness were reduced in male, but not female, tumor-bearing mice compared to vehicle-injected control mice. Cardiac protein synthesis was reduced in tumor-bearing male mice compared to control mice (p = 0.025). Aspect ratio and form factor of cardiac mitochondria from the tumor-bearing mice were increased compared control mice (p = 0.042 and p = 0.0032, respectively) indicating a more fused mitochondrial network in the hearts of tumor-bearing mice. In cultured cardiomyocytes maximal oxygen consumption and mitochondrial reserve capacity were reduced in cells exposed to tumor cell-conditioned medium compared to non-conditioned medium (p = 0.0059, p = 0.0010). Whole transcriptome sequencing of cardiac ventricular muscle from tumor-bearing vs. control mice showed altered expression of 1648 RNA transcripts with a false discovery rate of less than 0.05. Of these, 54 RNA transcripts were reduced ≤ 0.5 fold, and 3 RNA transcripts were increased by ≥1.5-fold in tumor-bearing mouse heart compared to control. Notably, the expression of mRNAs for apelin (Apln), the apelin receptor (Aplnr), the N-myc proto-oncogene, early growth protein (Egr1), and the transcription factor Sox9 were reduced by >50%, whereas the mRNA for growth arrest and DNA-damage-inducible, beta (Gadd45b) is increased >2-fold, in ventricular tissue from tumor-bearing mice compared to control mice. CONCLUSIONS: Lung tumor cells induce heart failure in male mice in association with reduced protein synthesis, mitochondrial function, and the expression of the mRNAs for inotropic and growth factors. These data provide new mechanistic insights into cancer-associated heart failure that may help unlock treatment options for this condition.
No takes yet. Share an insight, caveat, or question.
Berent et al. (2019) studied Cancer-associated heart failure. Lewis lung carcinoma (LLC1) cells vs. PBS vehicle was evaluated on Cardiac ejection fraction (Teichholz method) in male mice (p=<0.0001).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: