TY - JOUR
T1 - Left ventricular extracellular matrix remodeling in dogs with right ventricular apical pacing
AU - Lin, Jih Min
AU - Lai, Ling Ping
AU - Lin, Chih Sheng
AU - Chou, Nai Kuan
AU - Chiu, Chih Yuan
AU - Lin, Jiunn Lee
PY - 2010/10/1
Y1 - 2010/10/1
N2 - Left Ventricular Remodeling in Pacing Dogs. Introduction: Right ventricle (RV) apical pacing is associated with increased incidence of heart failure due to left ventricle (LV) desynchronization. We aim to investigate extracellular matrix (ECM) remodeling of the LV in dogs with atria-sensed RV apical pacing. Methods and Results: Dogs with pacemakers underwent AV nodal ablation. After 12 weeks of atria-sensed obligatory RV pacing, LVs were separated into septum and lateral wall for analysis. Zymographic activity, including matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-3, collagen transcript expression, and histology were examined in opposite portions of the LV to identify possible ECM remodeling changes by RV apical pacing. Compared with sham-operated dogs, increased interstitial fibrosis and fragmentation of myofibrils was found in the LV lateral wall in the pacing group. Collagen type II mRNA showed a significant 2-fold increase in the LV lateral wall in the pacing group. Although collagen type I mRNA was increased, the difference was not significant. Zymography demonstrated MMP-9 activity was enhanced in both the LV lateral wall and septum in the pacing group, but MMP-2 activity was enhanced in the LV lateral wall. Immunfluorescence stain confirmed the activation of MMP-2 and MMP-9 in the LV lateral wall in the pacing group. Protein expression of TIMP-1 and TIMP-3 showed regional differences in the pacing group and both proteins were increased in the LV lateral wall. Conclusion: LV dyssynchrony by RV apical pacing elicits heterogeneous ECM remodeling in the LV. These findings assist in the elucidation of the pathophysiology of LV desynchronization. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1142-1149)
AB - Left Ventricular Remodeling in Pacing Dogs. Introduction: Right ventricle (RV) apical pacing is associated with increased incidence of heart failure due to left ventricle (LV) desynchronization. We aim to investigate extracellular matrix (ECM) remodeling of the LV in dogs with atria-sensed RV apical pacing. Methods and Results: Dogs with pacemakers underwent AV nodal ablation. After 12 weeks of atria-sensed obligatory RV pacing, LVs were separated into septum and lateral wall for analysis. Zymographic activity, including matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-3, collagen transcript expression, and histology were examined in opposite portions of the LV to identify possible ECM remodeling changes by RV apical pacing. Compared with sham-operated dogs, increased interstitial fibrosis and fragmentation of myofibrils was found in the LV lateral wall in the pacing group. Collagen type II mRNA showed a significant 2-fold increase in the LV lateral wall in the pacing group. Although collagen type I mRNA was increased, the difference was not significant. Zymography demonstrated MMP-9 activity was enhanced in both the LV lateral wall and septum in the pacing group, but MMP-2 activity was enhanced in the LV lateral wall. Immunfluorescence stain confirmed the activation of MMP-2 and MMP-9 in the LV lateral wall in the pacing group. Protein expression of TIMP-1 and TIMP-3 showed regional differences in the pacing group and both proteins were increased in the LV lateral wall. Conclusion: LV dyssynchrony by RV apical pacing elicits heterogeneous ECM remodeling in the LV. These findings assist in the elucidation of the pathophysiology of LV desynchronization. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1142-1149)
KW - dyssynchrony
KW - heart failure
KW - matrix metalloproteinase
KW - remodeling
KW - ventricular pacing
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U2 - 10.1111/j.1540-8167.2010.01765.x
DO - 10.1111/j.1540-8167.2010.01765.x
M3 - Article
C2 - 20384649
AN - SCOPUS:78649287602
SN - 1045-3873
VL - 21
SP - 1142
EP - 1149
JO - Journal of Cardiovascular Electrophysiology
JF - Journal of Cardiovascular Electrophysiology
IS - 10
ER -