Cancer Therapy-related Cardiotoxicity is Associated with Distinct Alterations of the Myocardial Lipidome

Figures

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  Figure 1. Characterisation of the global myocardial lipidome in AIC. (A) Principal component analysis (PCA) of filtered lipid species. (B) Bubble graph showing log2(fold change) of lipid species in AIC versus controls (filtered for adjusted p‐value < 0.1). Bubble size is inversely proportional to p‐value. Colour represents lipid class. Species above horizontal dashed line (at log2[fold change] = 0) are increased in AIC, below decreased. (C) Volcano plot of all lipid species. Blue shows significantly and differentially down‐regulated lipid species, red significantly and differentially up‐regulated species. Orange shows significantly but not differentially altered species. Horizontal dashed line at adjusted p‐value = 0.05, all species above the line are significantly altered. Vertical dashed lines at 1 and −1 log2(fold change), lipid species outside of these lines show differential divergence. (D) Bar graph showing the fold change of lipid classes in AIC versus control. Colour represents the adjusted p‐value, deeper blue depicting lower adjusted p‐values. CE, cholesterol ester; Cer, ceramide; Chol, cholesterol; CL, cardiolipin; DAG, diacylglycerol; GL, glycerolipid; GPL, glycerophospholipid;…

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  Figure 2. Most active reactions of lipid classes in AIC (generated with Lipid MAPS' BioPan).

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  Figure 3. Characterisation of fatty acid carbon chain length and double bonds. (A) Schematic illustration of carbon chain length and number of carbon–carbon double bonds as chemical features of fatty acids. (B) Number of carbon double bonds in AIC and controls. (C) Comparison of fatty acid abundance according to carbon chain length. Displayed is the proportion of fatty acids in AIC patients relative to controls. *p < 0.05, **p < 0.01, ****p < 0.0001, using Wilcoxon rank test, adjusted for multiple testing using false discovery rate method of Benjamini and Hochberg (B and C).

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  Figure 4. Lysolipids are significantly altered in AIC. (A) Principal component (PC) analysis of lysolipid species (filtered). (B) Boxplot showing mole‐percent lysolipids of total lipid content. There is a significant increase in lysolipids in AIC. (C) Relative proportion of the lysolipid classes AIC versus control.

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  Figure 5. Specific lipid alterations in AIC compared to other heart failure aetiologies (oHF). (A) Cuneiform plot of the measured lipid classes in three comparisons: AIC versus control, AIC versus oHF, and oHF versus control. (B) Total lysolipid content, relative to the lysolipid content of the control group (= 1, dashed line). (C) Boxplot of lipid classes in AIC compared to oHF in mole% of total lipid content.