Anti-Inflammatory Effects of Ang-(1-7) Bone-Targeting Conjugate in an Adjuvant-Induced Arthritis Rat Model

Figures

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  Figure 1. Schematic overview of the RAS. Ang—angiotensin, ACE—angiotensin-converting enzyme, ACE2—angiotensin-converting enzyme 2, MasR—Mas receptor, AT1R—angiotensin II type 1 receptor, AT2R—angiotensin II type 2 receptor.

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  Figure 2. Effect of adjuvant-induced arthritis and treatment with Ang-(1-7) and Ang. Conj. on the percentage change of body weight (A) and the arthritis index values during the study period (B). The percentage change in the right joint (C), right paw (D), left joint (E), and left paw (F) diameters compared to day 0. The number of animals in control and inflamed groups were six and in Ang-(1-7) and Ang. Conj.-treated groups were five. The values are reported as mean ± SEM, and statistical analysis was done using one-way ANOVA with the Tukey multiple comparison post-hoc test. Groups labeled with different letters have significant differences between them (p < 0.05).

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  Figure 3. Effect of adjuvant-induced arthritis and Ang-(1-7) or Ang. Conj. treatment on serum NO concentrations at the end of the experiment. The number of animals in control and inflamed groups were six, and in Ang-(1-7) and Ang. Conj.-treated groups were five. The values are reported as mean ± SEM, and statistical analysis was done using one-way ANOVA with the Tukey multiple comparison post-hoc test. Groups labeled with different letters have significant differences between them (p < 0.05).

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  Figure 4. The plasma concentration of Ang-(1-7) (A), Ang II (B), and their ratio (C) in control (n = 6), inflamed (n = 6), Ang-(1-7)-treated (n = 5), and Ang. Conj.-treated (n = 5) groups. The values are reported as mean ± SEM, and statistical analysis was done using one-way ANOVA with the Tukey multiple comparison post-hoc test. Groups labeled with different letters have significant differences between them (p < 0.05).

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  Figure 5. Gene expression of ACE1, ACE2, MasR, and AT1R levels in the heart (A), lung (B), liver (C), kidney (D) tissues, and the ratio of ACE2/ACE1 and MasR/AT1R in those tissues (E) in control (n = 6), inflamed (n = 6), Ang-(1-7)-treated (n = 5), and Ang. Conj.-treated (n = 5) groups. ACE1—angiotensin-converting enzyme 1, ACE2—angiotensin-converting enzyme 2, MasR—Mas receptor, AT1R—angiotensin II type 1 receptor. The values are reported as mean ± SEM, and statistical analysis was done using one-way ANOVA with the Tukey multiple comparison post-hoc test. Groups labeled with different letters have significant differences between them (p < 0.05).

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  Figure 6. Protein expression of ACE1, ACE2, MasR, and AT1R, levels in the heart (A), lung (B), liver (C), kidney (D) tissues, and the ratio of ACE2/ACE1 and MasR/AT1R (E) in control (n = 6), inflamed (n = 6), Ang-(1-7)-treated (n = 5), and Ang. Conj.-treated (n = 5) groups. ACE1—angiotensin-converting enzyme 1, ACE2—angiotensin-converting enzyme 2, MasR—Mas receptor, AT1R—angiotensin II type 1 receptor. The values are reported as mean ± SEM, and statistical analysis was done using one-way ANOVA with the Tukey multiple comparison post-hoc test. Groups labeled with different letters have significant differences between them (p < 0.05).