Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure
Abstract
:1. Introduction
2. Results and Discussion
2.1. Echocardiographic Indices
Parameters | Sham ( n = 10) | MI ( n = 10) | MI-Simvastatin ( n = 10) |
---|---|---|---|
EF, % | 83.0 ± 7.6 | 30.0 ± 16.1 * | 43.0 ± 21.5 * |
FS, % | 48.5 ± 8.8 | 12.7 ± 7.5 * | 20.6 ± 15.2 * |
LVEDD, mm | 7.9 ± 0.6 | 9.5 ± 1.3 ** | 9.6 ± 1.6 *** |
LVESD, mm | 4.0 ± 0.8 | 8.3 ± 1.5 * | 7.8 ± 2.2 * |
LAD, mm | 3.4 ± 0.8 | 3.8 ± 0.9 | 3.6 ± 0.8 |
2.2. Atrial Fibrillation Induction Study
2.3. Reduction of Atrial Fibrosis by Simvastatin
2.4. Expression of Nitric Oxide Synthases and Calcium Handling Proteins
Parameters | Sham ( n = 10) | MI ( n = 10) | MI-Simvastatin ( n = 10) |
---|---|---|---|
Fibrosis (%) | 0.24 ± 0.09 ( n = 7) | 2.30 ± 0.71 * ( n = 7) | 1.17 ± 0.16 # ( n = 7) |
eNOS | 13.41 ± 2.58 ( n = 6) | 6.75 ± 2.05 * ( n = 6) | 12.06 ± 3.43 # ( n = 6) |
iNOS | 0.28 ± 0.30 ( n = 9) | 7.33 ± 5.79 * ( n = 10) | 1.60 ± 1.47 **,# ( n = 12) |
INCX | 0.79 ± 0.48 ( n = 8) | 14.52 ± 11.87 * ( n = 11) | 4.19 ± 11.87 *,## ( n = 12) |
SERCA | 30.90 ± 3.18 ( n = 6) | 21.13 ± 1.36 * ( n = 6) | 25.43 ± 3.27 **,## ( n = 6) |
TM | 2.54 ± 0.47 ( n = 6) | 0.80 ± 0.28 * ( n = 6) | 1.85 ± 0.38 # ( n = 6) |
TFPI | 6.37 ± 0.71 ( n = 6) | 3.15 ± 0.22 ( n = 6) | 4.32 ± 0.47 ( n = 6) |
tPA | 2.73 ± 0.12 ( n = 6) | 1.25 ± 0.12 ( n = 6) | 2.01 ± 0.13 ( n = 6) |
Rac 1 | 16,165 ± 1696 ( n = 6) | 28,440 ± 1655 * ( n = 6) | 19,275 ± 2236 # ( n = 5) |
2.5. Immunohistochemistry Results
2.6. Thrombogenicity and Rac 1 Activity
3. Experimental Section
3.1. Animals Models
3.2. Echocardiogram
3.3. Electrophysiological Study
3.4. Quantification of Fibrosis
3.5. Western Blot
3.6. Rac1 GST-p21-Activated Kinase Pull-Down Assay
3.7. Immunohistochemistry for eNOS and iNOS
3.8. Statistical Analysis
4. Conclusions
Author Contributions
Conflicts of Interest
References
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Cho, K.-I.; Koo, S.-H.; Cha, T.-J.; Heo, J.-H.; Kim, H.-S.; Jo, G.-B.; Lee, J.-W. Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure. Int. J. Mol. Sci. 2014, 15, 14803-14818. https://doi.org/10.3390/ijms150814803
Cho K-I, Koo S-H, Cha T-J, Heo J-H, Kim H-S, Jo G-B, Lee J-W. Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure. International Journal of Molecular Sciences. 2014; 15(8):14803-14818. https://doi.org/10.3390/ijms150814803
Chicago/Turabian StyleCho, Kyoung-Im, Sang-Ho Koo, Tae-Joon Cha, Jung-Ho Heo, Hyun-Su Kim, Gee-Bum Jo, and Jae-Woo Lee. 2014. "Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure" International Journal of Molecular Sciences 15, no. 8: 14803-14818. https://doi.org/10.3390/ijms150814803