Local microRNA-133a Downregulation is Associated with Hypertrophy in the Dyssynchronous Heart

Figures

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  Figure 1. Magnetic resonance imaging‐derived left ventricular (LV) volumes and strains at the end of the protocol (at 4 months) in the three groups: control; left bundle branch block (LBBB) and LBBB + cardiac resynchronization therapy (CRT). Panel (A) LV end diastolic volume (EDV); panel (B) LV wall volume. Panels (C), (D), and (E) typical examples of strain patterns in control, LBBB, and CRT septum (dashed lines) and LV free wall (LVfw; solid lines). Note the discoordinated contraction during LBBB with pre‐stretch of the LVfw (1) and septal rebound stretch (2). Time of aortic valve opening (AvO) and closure (AvC) are depicted by dashed vertical lines. Panel (F) circumferential strain in the septum and LVfw as percentage of mean strain of the total LV. In panels (A), (B), and (F), the line within each box indicates the median value, the upper and lower margins of the box, the 25th–75th percentile, and the bars the minimum and maximum value. *P < 0.05 vs. equivalent region in control; †P < 0.05 vs. septum in same heart; ‡P < 0.05 vs. same region in LBBB group.

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  Figure 2. Left ventricular geometric changes due to left bundle branch block (LBBB) and LBBB + cardiac resynchronization therapy (CRT), expressed as percentage change from baseline. Panel (A) wall thickness of the septum (circles) and left ventricular free wall (LVfw; squares) in LBBB (black filled symbols) and LBBB+CRT (open symbols) dogs. Panel (B) LVfw/septal wall thickness ratio in LBBB (black filled symbols) and LBBB+CRT (open symbols) dogs. Panel (C) end diastolic volume in LBBB (black filled symbols) and LBBB+CRT (open symbols) dogs. *P < 0.05 vs. baseline (month 0); †P < 0.05 vs. month 2; ‡P < 0.05 vs. LBBB. Presented are median values and 25th or 75th percentile to on‐side only for clarity.

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  Figure 3. Panel (A) representative examples of the modified azan staining in the septum and left ventricular free wall (LVfw) in the same heart of a LBBB dog (magnification is equal between the slices). Panel (B) cardiomyocyte diameter in the septum and LVfw in the control, left bundle branch block (LBBB), and LBBB + cardiac resynchronization therapy (CRT) group. Data in panel (B) are presented as median (the line within each box), the upper and lower margins of the box are the 25th–75th percentile and the bars the minimum and maximum value, *P < 0.05 vs. corresponding region in control; †P < 0.05 vs. septum in the same heart.

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  Figure 4. Relative miR‐133a [panel (A)] and connective tissue growth factor (CTGF) expression [panel (B)] in the septum and left ventricular free wall (LVfw) in the control, left bundle branch block (LBBB), and LBBB + cardiac resynchronization therapy (CRT) group. Data are presented as median (the line within each box), the upper and lower margins of the box are the 25th–75th percentile and the bars the minimum and maximum value. *P < 0.05 vs. equivalent region in control; †P < 0.05 vs. septum in the same heart.

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  Figure 5. Relative expression of miR‐29c [panel (A)], miR‐30c [panel (B)], and collagen type 1 [COL1A1; panel (C)] in the septum and left ventricular free wall (LVfw) in the control, left bundle branch block (LBBB), and LBBB + cardiac resynchronization therapy (CRT) group. Relative change in collagen concentration based on the Sircol assay [panel (D)] and on Sirius Red histology [panel (E)], with representative examples of septal and LVfw sections of a LBBB dog [panel (F)]. Data in panels (A–E) are presented as median (the line within each box), the upper and lower margins of the box are the 25th–75th percentile, and the bars the minimum and maximum value, *P < 0.05 vs. equivalent region in control.

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  Figure 6. Relation between expression of miR‐133a and its target genes connective tissue growth factor [CTGF; panel (A)], nuclear factor of activated T cells [NFATc4; panel (B)], and serum response factor [SRF; panel (C)]. Squares, control; triangles, left bundle branch block (LBBB); diamonds, cardiac resynchronization therapy (CRT) group. Solid symbols, left ventricular free wall; open symbols, septum. Pearson r and P values are based on all the individual data points; for clarity, only median values and 25th–75th percentile (bars) are depicted.