Int J Med Sci 2013; 10(7):812-824. doi:10.7150/ijms.5931 This issue Cite

Research Paper

Angiotensin Receptor Blockers and Statins Could Alleviate Atrial Fibrosis via Regulating Platelet-Derived Growth Factor/Rac1 /Nuclear Factor-Kappa B Axis

Dongfang Yang1,*, Jia Yuan1,*, Gan Liu1,2, Zhiyu Ling1, Haiyan Zeng3, Yunqing Chen1, ✉, Yue Zhang1, Qiang She1, Xue Zhou4

1. Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China;
2. Department of Cardiology, The People's Hospital of Hechuan District, Chongqing, China;
3. Department of Epidemiology and Health Statistics, The Public Health College of Huaxi of Sichuan University, Sichuan, China;
4. Department of cardiology, Children's hospital of Chongqing Medical University, Chongqing, China.
* Dongfang Yang and Jia Yuan contributed equally to this work.

Citation:
Yang D, Yuan J, Liu G, Ling Z, Zeng H, Chen Y, Zhang Y, She Q, Zhou X. Angiotensin Receptor Blockers and Statins Could Alleviate Atrial Fibrosis via Regulating Platelet-Derived Growth Factor/Rac1 /Nuclear Factor-Kappa B Axis. Int J Med Sci 2013; 10(7):812-824. doi:10.7150/ijms.5931. https://www.medsci.org/v10p0812.htm
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Abstract

Aims: To investigate whether the administration of renin-angiotensin system (RAS) inhibitors and statins could alleviate atrial fibrosis via platelet-derived growth factor (PDGF)/Rac1 /nuclear factor-kappa B (NF-κB) axis.

Methods and Results: In human left atrium, the degree of atrial fibrosis, as well as the expression levels of PDGF, Rac1 and NF-κB increased 1.5 to 2.9 folds in patients with atrial fibrillation compared to that with sinus rhythm, (P<0.0001). There were strongly positive correlations between angiotensin II (Ang II) or procollagen type III-alpha-1 (COL3A1) with PDGF, Rac1, NF-κB, and among PDGF, Rac1 and NF-κB (all P<0.05). At 3 weeks after the transverse aorta constriction (TAC) operation in rat model and with intervention of irbesartan or/and simvastatin, the collagen volume fraction (CVF) and atrial natriuretic peptide (ANP) values respectively increased 6-folds and 3.5-folds in the TAC group compared to SHAM group (P<0.0001), but these levels decreased by 16% to 63% with following drug intervention (all P<0.0001), the combined treatment was the lowest. Accordingly, the expression levels of PDGF (3-folds), Rac1 (1.6-folds), NF-κB (7-folds) and AngII (12-folds) significantly increased in the TAC group compared to the SHAM group, and these levels were also reduced by 25% to 64% with following drug intervention. The highest reduction could be seen after treatment with irbesartan and simvastatin in combination (all P<0.001).There were strongly positive correlations between AngII or CVF with PDGF, Rac1, NF-κB, and among PDGF, Rac1 and NF-κB (all P<0.05).

Conclusions: Irbesartan or/and simvastatin can improve atrial fibrosis by regulating PDGF/Rac1/NF-κB axis.

Keywords: atrial fibrosis, platelet-derived growth factor (PDGF), Rac1, nuclear factor-kappa B (NF-κB), Irbesartan, Simvastatin.


Citation styles

APA
Yang, D., Yuan, J., Liu, G., Ling, Z., Zeng, H., Chen, Y., Zhang, Y., She, Q., Zhou, X. (2013). Angiotensin Receptor Blockers and Statins Could Alleviate Atrial Fibrosis via Regulating Platelet-Derived Growth Factor/Rac1 /Nuclear Factor-Kappa B Axis. International Journal of Medical Sciences, 10(7), 812-824. https://doi.org/10.7150/ijms.5931.

ACS
Yang, D.; Yuan, J.; Liu, G.; Ling, Z.; Zeng, H.; Chen, Y.; Zhang, Y.; She, Q.; Zhou, X. Angiotensin Receptor Blockers and Statins Could Alleviate Atrial Fibrosis via Regulating Platelet-Derived Growth Factor/Rac1 /Nuclear Factor-Kappa B Axis. Int. J. Med. Sci. 2013, 10 (7), 812-824. DOI: 10.7150/ijms.5931.

NLM
Yang D, Yuan J, Liu G, Ling Z, Zeng H, Chen Y, Zhang Y, She Q, Zhou X. Angiotensin Receptor Blockers and Statins Could Alleviate Atrial Fibrosis via Regulating Platelet-Derived Growth Factor/Rac1 /Nuclear Factor-Kappa B Axis. Int J Med Sci 2013; 10(7):812-824. doi:10.7150/ijms.5931. https://www.medsci.org/v10p0812.htm

CSE
Yang D, Yuan J, Liu G, Ling Z, Zeng H, Chen Y, Zhang Y, She Q, Zhou X. 2013. Angiotensin Receptor Blockers and Statins Could Alleviate Atrial Fibrosis via Regulating Platelet-Derived Growth Factor/Rac1 /Nuclear Factor-Kappa B Axis. Int J Med Sci. 10(7):812-824.

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