Characterization of atrial and ventricular remodeling in an improved minimally invasive mouse model of transverse aortic constriction

Figures

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  Figure 1.. Overview of minimally invasive transverse aortic constriction (mTAC) model. (A) A schematic illustration of the incision exposing the aortic arch and ligation site. (B) Flow chart of the mTAC surgical model with time points for echocardiography (echo). (C) Procedure-derived mortality during mTAC surgery in sham (n = 6) and mTAC mice (n = 11). (D) Survival Kaplan-Meier curve for sham (black line, n = 6) and mTAC (red line, n = 10) mice during the 8-week postoperative (post-op) period. The student’s t-test was used to compare procedure-derived mortality and the Mantel-Cox test was used for survival Kaplan-Meier curve comparison.

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  Figure 2.. Effectiveness of aortic constriction in the mTAC model. (A) Representative echocardiography images of the aortic arch in sham (left panel) and mTAC (right panel) mice, showing the constriction (red arrow) of the aorta (Ao). (B) Schematic illustration of the aortic arch and representative recording of blood flow in right carotid (RC; upper panels) and left carotid (LC; bottom panels) from sham (left) and mTAC (right) mice. (C) Quantification of RC/LC ratios in sham (n = 6) versus mTAC (n = 8) mice. Data shown mean ± SEM. ***P < 0.001 using student’s t-test.

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  Figure 3.. Heart failure with reduced ejection fraction induced by mTAC. (A) Representative M-mode echocardiography tracings from the left ventricle of sham (upper panels) and mTAC mice (bottom panels) at baseline and 2, 4, 6, and 8 weeks after surgery. (B) Average ejection fraction (EF) at the different time points in sham (black plots, n = 6) and mTAC (red plots, n = 8) mice. (C) Individual EF changes in mTAC mice at different time points. (D-G) Average of (D) fractional shortening (FS), (E) end-diastolic diameter (EDD), (F) end-systolic diameter (ESD), (G) left ventricular posterior wall at diastole (LVPW;d), and (H) LVPW in systole (LVPW;s), at the different timepoints in sham and mTAC mice. Data shown mean ± SEM. *P < 0.05, **P < 0.01 and ***P < 0.001, using 2-way ANOVA with Bonferroni’s multiple-comparision correction.

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  Figure 4.. Preserved right ventricular function in mTAC mice. (A) Representative Doppler traces of pulmonary artery flow in sham (left panel) and mTAC mice (right panel). (B-D) Average values of (B) pulmonary vein artery velocity (PAV), (C) peak gradient (PAPG), and (D) velocity time integral (VTI) in sham (black dots, n = 6) and mTAC mice (red dots, n = 7). Data shown mean ± SEM. Student’s t-test was used to compare sham and mTAC groups.

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  Figure 5.. Left atrial remodeling and dysfunction in mTAC model. (A) Representative long-axis echocardiography data of sham (left panel) and mTAC mice (right panel) showing the aorta (Ao), and left atrium (LA). (B) Average value of LA size in sham (black dots, n = 6) and mTAC mice (red dots, n = 7). (C) Representative Doppler traces of mitral valve blood flow velocity showing early (E) and atrial (A) waves in sham (left panel) and mTAC mice (right panel). (D) Average of mitral early to atrial waves (E/ A) ratio in sham (black dots, n = 6) and mTAC (red dots, n = 7). Data shown mean ± SEM. **P < 0.01 using student’s t-test.

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  Figure 6.. Left ventricular remodeling induced by mTAC. (A and B) Quantification of heart weight to body weight (HW/BW) (A) and heart weight to tibia length ratios (HW/TL) (B) in mTAC versus sham mice. Quantification of NPPA (C) and NPPB (D) mRNA expression in mTAC vs. sham hearts. (E) Masson trichrome staining of fibrosis in the whole heart (upper panels) and left ventricular histological sections (bottom panels) in sham (left panels) and mTAC mice (right panels). (F) Quantification of left ventricular fibrosis in sham and mTAC mice. Data shown mean ± SEM. *P < 0.05 and **P < 0.01 using student’s t-test.