Targeted proteomic analyses during combined angiotensin-converting enzyme inhibitor and mineralocorticoid receptor antagonist administration (CARDALIS®) in healthy dogs

Figures

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  Figure 1. Schematic representation of experimental design and timeline of sampling. There are 4 sampling days: BAS1 (before experimental RAAS activation with low‐sodium diet), BAS2 (after 5 days of low‐sodium diet), DOS1 (after first dose of benazepril/spironolactone [CARDALIS®]), and DOS14 (after 14 days of dosing). Three groups (n = 6 dogs each) received different doses of benazepril/spironolactone. Colored circles indicate purpose and timing of blood samples collected on each sampling day. Reproduced with permission from https://pubmed.ncbi.nlm.nih.gov/39601373/. Abbreviation: RAAS = renin–angiotensin–aldosterone system.

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  Figure 2. Volcano plot showing differences in proteomic biomarker concentrations at the 2-h timepoint for BAS2 vs BAS1, representing the effects of experimental RAAS activation with 5 days of low-sodium diet consumption. The Y-axis represents −log10 of P-values for group differences; horizontal dashed lines represent P-value cutoffs of < .1 (lower) and < .05 (upper). The X-axis represents fold-differences in biomarker concentration between timepoints such that values below 1.0 indicate downregulation, whereas values above 1.0 indicate upregulation. Abbreviation: RAAS = renin–angiotensin–aldosterone system.

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  Figure 3. Scatterplots displaying individual dog results (gray lines) and group mean (yellow line) with complete protein dynamics across sampling timepoints (0, 2, 4, 10, 16, and 20 h) for selected biomarkers demonstrating significant differences between sampling days. (A) Concentrations of ACE2 and FGF-5 at sampling days BAS1 and BAS2 (effect of experimental RAAS activation); (B) concentrations of LIF and TSLP at sampling days BAS2 and DOS1 (effect of single-dose benazepril/spironolactone [CARDALIS®]). Biomarker concentrations are shown in NPX values. See Tables 1 and 2 for P-values and fold-differences in mean biomarker concentration between sampling days. Abbreviations: NPX = normalized protein expression; RAAS = renin–angiotensin–aldosterone system.

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  Figure 4. Volcano plot showing differences in proteomic biomarker concentrations at the 2-h timepoint for DOS1 vs BAS2, representing the effects of single-dose benazepril/spironolactone (CARDALIS) treatment. The Y-axis represents −log10 of P-values for group differences; horizontal dashed lines represent P-value cutoffs of < .1 (lower) and < .05 (upper). The X-axis represents fold-differences in biomarker concentration between timepoints such that values below 1.0 indicate downregulation, whereas values above 1.0 indicate upregulation.

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  Figure 5. Volcano plot showing differences in proteomic biomarker concentrations at the 2-h timepoint for DOS14 vs BAS2, representing the effects of repeated-dose (steady state) benazepril/spironolactone (CARDALIS) treatment. The Y-axis represents −log10 of P-values for group differences; horizontal dashed lines represent P-value cutoffs of < .1 (lower) and < .05 (upper). The X-axis represents fold-differences in biomarker concentration between timepoints such that values below 1.0 indicate downregulation, whereas values above 1.0 indicate upregulation.