Knockout of Trpa1 accelerates age-related cardiac fibrosis and dysfunction

Figures

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  Fig 1. The TRPA1 protein level in the heart from older mice is decreased. The protein levels of TRPA1 were measured by Western blotting in the myocardial tissue from 12-week-old (young) and 52-week-old (older) wild-type mice. Data are mean ± SE. n = 4 per group. **P<0.01 vs. 12-week-old mice.

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  Fig 2. Knockout of Trpa1 enhances age-related left ventricular dilation and dysfunction. (A) Representative M-mode echocardiograms of 12-week-old (young) and 52-week-old (older) Trpa1-/- mice and WT littermates. The left ventricular posterior wall thickness at end-diastole (LVPWd) (B), left ventricular posterior wall thickness at end-systole (LVPWs) (C), left ventricular anterior wall thickness at end-diastole (LVAWd) (D), left ventricular anterior wall thickness at end-systole (LVAWs) (E), left ventricular internal dimension at end-diastole (LVIDd) (F), left ventricular internal dimension at end-systole (LVIDs) (G), left ventricular volume at end-diastole (LV Vol, d) (H), left ventricular volume at end-systole (LV Vol, s) (I), left ventricular ejection fraction (LVEF) (J), left ventricular fractional shortening (LVFS) (K), mitral E/A ratio (L), and isovolumetric relaxation time (IVRT) (M) of 12-week-old and 52-week-old Trpa1-/- mice and WT littermates were measured by echocardiography. Data are mean±SE of 10 mice in each older mouse group and 6 mice in each young mouse group. *P<0.05, **P<0.01 vs. 12-week-old congenic mice; #P<0.05, ##P<0.01 vs. 52-week-old WT mice.

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  Fig 3. Knockout of Trpa1 exacerbates age-related cardiac fibrosis. Representative H&E-stained whole-heart cross-sections (A) and H&E-stained (B) and Picrosirius red-stained (C) left ventricular sections of 12-week-old and 52-week-old Trpa1-/- mice and WT littermates. (D) Left ventricular mass was evaluated by echocardiography. Cross-sectional area of cardiomyocytes (E) and collagen deposition fraction (F) were quantified based on H&E and PSR staining, respectively. Data are mean±SE of 6 mice in each group. *P<0.05, **P<0.01 vs. 12-week-old congenic mice; #P<0.05 vs. 52-week-old WT mice.

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  Fig 4. Knockout of Trpa1 alters expression of fibrosis-related genes. Differently expressed genes (A), gene expression of collagens (B), and gene expression of matrix metalloproteinases (C) in the heart tissue 12-week-old and 52-week-old Trpa1-/- mice and WT littermates were measured by quantitative PCR array assays. Data are mean±SE of 3 samples in each group. *P < 0.05, **P < 0.01 vs. 52-week-old WT mice.