Female rats with severe left ventricle volume overload exhibit more cardiac hypertrophy but fewer myocardial transcriptional changes than males

Figures

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  Figure 1. Progression of different LV parameters as evaluated by echocardiography during the duration of the study (26 weeks). Δ: % difference between week 0 and week 26, EDD: end-diastolic diameter (A), ESD: end-systolic diameter (B), SW: septal wall thickness (C), PW: posterior wall thickness (D), RWT: relative wall thickness (E), mWS: mean wall stress (F), FS: fractional shortening (G), SV: stroke volume (H) and CO: cardiac output (I). The results are reported in % as the mean ± SEM (n = 7–11/gr). Probability values from a 2-way ANOVA and Holm-Sidak post-testing to evaluate the p value of sex, (S), disease (D) or disease-sex interactions (S × D) are shown next to each panel.

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  Figure 2. Impact of LV dilatation and hypertrophy caused by severe aortic regurgitation on cardiomyocyte cross-sectional area (Top panels; A and B) and on myocardial capillary density (bottom panels (C and D). Left panels (A and C): The results are expressed as the mean ± SEM (n = 6–7/gr.). Probability values are from a 2-way ANOVA and Holm-Sedak post-testing. *p < 0.05 or **p < 0.01 between indicated groups. Upper right panels: Representative Masson’s trichrome staining of mid-chamber short-axis LV sections (magnification x200); bottom right panels: LV sections stained with isolectin B4 coupled with horseradish peroxidase (magnification x400).

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  Figure 3. Evaluation by real-time quantitative RT-PCR of the LV mRNA levels of various hypertrophy (top two graphs; A and B) and extracellular matrix remodelling (bottom; C) markers. The results are reported in arbitrary units (AU) as the mean ± SEM (n = 5–6/gr.). The mRNA levels of the sham (sham-operated animals) groups (ShM and ShF) were normalized to 1 and are represented by the dotted line. White columns represent the ArM group, and black columns represent the ArF group. *p < 0.05 vs. the corresponding sham group and ¶p < 0.05 between the ArM and ArF groups.

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  Figure 4. LV myocardial activity levels of enzymes implicated in fatty acid β-oxidation, glucose metabolism and mitochondrial energy production in male and female AR rats after 6 months. Hydroxyacyl-Coenzyme A dehydrogenase (HADH) (A), hexokinase (HK) (B), citrate synthase (C), and succinate dehydrogenase (D) enzymatic activities were measured in LV homogenates from 5–6 animals in each group as described in the Methods. The results are reported as the mean ± SEM. Probability values are from a 2-way ANOVA and Holm-Sedak post-testing. *p < 0.05 and **p < 0.01 between indicated groups.

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  Figure 5. Evaluation by real-time quantitative RT-PCR of the LV mRNA levels of genes encoding for enzymes implicated in fatty acid oxidation (left panels; A and C) and glycolysis (top right panel; B) and for transcription factors related to bioenergetics control (right bottom panel; D). The results are reported in arbitrary units (AU) as the mean ± SEM (n = 5–6/gr.). The mRNA levels of the sham (sham-operated animals) groups (ShM and ShF) were normalized to 1 and are represented by the dotted line. White columns represent the ArM group, and black columns represent the ArF group. *p < 0.05 vs. the corresponding sham group and ¶p < 0.05 between the ArM and ArF groups.

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  Figure 6. Evaluation by real-time quantitative RT-PCR of the LV mRNA levels of genes encoding for markers of mitochondrial biogenesis and function (A and B). The results are reported in arbitrary units (AU) as the mean ± SEM (n = 5–6/gr.). The mRNA levels of the sham (sham-operated animals) groups (ShM and ShF) were normalized to 1 and are represented by the dotted line. White columns represent the ArM group, and black columns represent the ArF group. *p < 0.05 vs. the corresponding sham group and ¶p < 0.05 between the ArM and ArF groups.