Fig 2: Prior exposure to low-dose DOX alone does not cause toxicity, in vivo (A) Experimental schematic of DOX dose response treatment paradigm. (B, C) Gravimetric measurements of (B) body weight and (C) heart weight normalized to tibia length (HW/TL). n = 6–7, data shown as mean ± SEM. “NS” denotes not significant. (D-E) Echocardiographic parameters after DOX dose response treatment paradigm for (D) ejection fraction, EF (%) and (E) Pulsed-wave and tissue Doppler at the mitral annulus, E/e’ ratio. n = 6–7, data shown as mean ± SEM. (F) RT-qPCR of select fibrosis genes Postn, Col1a1, and Col3a1 in LV extracts after DOX dose response treatment paradigm. n = 4–5, data shown as mean ± SEM, data are NS. (G-J) RT-qPCR of select genes in LV extracts after chronic DIC paradigm shown in Fig. 6: (G) Col3a1, (H) Myh7, (I) Atp2a2, and (J) Nppb. n = 5–6, data shown as mean ± SEM. # p ≤ 0.05; ## p ≤ 0.01 versus Saline by ANOVA with Tukey's multiple comparisons test.

Fig 3: Acute low-dose DOX alters the CFB transcriptome. (A) Quantitative real-time polymerase chain reaction (RT-qPCR) of select fibrosis genes (Postn, Fn1, Col1a1, and Col3a1) in CFB after acute DOX treatment. n = 3, data shown as mean ± SEM, * p ≤ 0.05 versus vehicle by unpaired t-test. (B) Heatmap of differentially expressed genes (DEGs). n = 3, p < 0.05, FDR < 0.05, log2 FC > 0.5. (C, D) Categorical analysis of DEGs displaying the top 10 significantly enriched (C) Gene Ontologies for Biological Processes and (D) KEGG Pathway terms.