Molecular Signatures of Sinus Node Dysfunction Induce Structural Remodeling in the Right Atrial Tissue.

Figures

• 

  Fig. 1. Cardiac dysfunctions induced by sinus node damage. (A) Average heart rate (HR) before the experimental sinus node damage (SNX; upper panel), and the duration (%) for which bradycardia is exhibited 7 days after SND induction (lower panel) in comparison with that in sham-operated controls (CTL). Sinus bradycardia was considered developed at HR < 130 bpm. Data are expressed as mean ± SEM (n = 3 for CTL and 5 for SNX groups; **P < 0.01 by t-test). (B) Increased fibrosis in the RA tissues by SNX. The RA sections were stained with H&E (upper panel) or MTS (lower panel). Scale bars = 50 µm.

• 

  Fig. 2. Genome-wide RNA expression profiles in RA tissues. (A) Venn diagram (upper panel) and heat map representation with hierarchical clustering (lower panel) of the differentially expressed genes (DEGs) examined 7 days after SNX. RNA levels of 143 genes were significantly higher in the sham-operated controls (CTLs), and 498 RNA levels were higher in the rabbits with SNX. (B) Heat map representation of the top 30 DEGs.

• 

  Fig. 3. Validation of the differential expression of selected mRNA species. qRT-PCR analyses of the selected DEGs categorized as secretory factors (a), membrane receptors and associated proteins (b), factors involved in extracellular matrix organization (c), actin cytoskeletal subunits (d), and other regulatory factors (e). Relative expression of each mRNA species was normalized to that of the average GAPDH, PPIA, and TBP expression and presented as mean ± SEM in arbitrary units (A.U.), for which the mean expression in the control (CTL) was defined as 1 (n = 3 for CTL [C] and 5 for SND [S] groups; *P < 0.05 and **P < 0.01 by unpaired t-test).

• 

  Fig. 4. Periostin and TGF-β 1 expression at protein levels in cardiac tissues. (A)Representativeimagesdepictingthe expressionofperiostin,TGF-β1,andβ-actinproteinsinvarious myocardial tissues as evaluated by immunoblot (RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle). (B) Expression ofperiostinandTGF-β1proteinsnormalizedtothatofβ-actin ispresentedasmean±SEMinarbitraryunits(A.U.),forwhich the mean expression in the control (CTL) was defined as 1 (n = 3 for CTL and 5 for the SNX groups; *P < 0.05 and **P < 0.01 by unpaired t-test).