Mildly Increased Renin Expression in the Absence of Kidney Injury in the Murine Transverse Aortic Constriction Model

Figures

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  FIGURE 1. Cardiac weight and function in TAC mice over time. A gradual increase in heart weight to tibia length ratio over time, indicating the presence of cardiac remodeling post-TAC (A). Stroke volume decreases over time post TAC vs. baseline (B). Mean ± SD. & = p < 0.0001. HW/TL; Heart weight/Tibia length.

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  FIGURE 2. Renal renin expression after TAC. Representative pictures of renin expression at baseline and after 3–70 days of TAC (A). Renin expression (depicted in brown) is visible in the juxtaglomerular cells close to the glomeruli (arrows). Renin expression, corrected for the number of glomeruli present in the section, is increased from day 35 compared to baseline (B). qPCR analysis of renin expression showed a trend of increased renin over time (C), 20 mice were excluded from the renin qPCR analysis as the levels were below the detection limit. In line with renal renin, the plasma renin concentration is increased significantly at 56–70 days post-TAC (D). A significant association between local and systemic renin is observed (r = 0.52, R2 = 0.27, p = < 0.001) (E). Mean ± SD, * = p < 0.05.

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  FIGURE 3. Plasma renin concentration increases upon reduced cardiac function. In line, the plasma renin levels are significantly correlated to a lower stroke volume after TAC (R2 = 0.45 and p = < 0.0001). SV; Stroke volume.

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  FIGURE 4. Kidney morphology, signs of damage and albumin levels. Urea levels in plasma were significantly upregulated over time after TAC versus baseline (A). No structural abnormalities were observed in glomeruli and tubuli (PAS staining) (B). No increase in urinary albumin (µg corrected for mM urinary creatinine) levels could be observed after TAC (C). Urine albumin levels (µg corrected for mM urinary creatinine) post-TAC were not different from baseline (metabolic cages) (D). Mean ± SD. #p < 0.05; & p < 0.01.

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  FIGURE 5. No kidney injury present based on qPCR analysis. Figure displays the relative expression of KIM-1 (A), CTGF (B), NGAL (C), TGF-β (D), and FN (E) at baseline (0) and over time post-TAC. No significant increase or decrease in mRNA expression is present, comparing post-TAC time points to the baseline animals.