Objective Plasma fibrinogen has been defined as a risk factor of cardiovascular disease and may play a role in the development of cardiac hypertrophy. We have previously demonstrated that the Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response protein 88 (MyD88)-dependent nuclear factor-κB (NF-κB) pathway is involved in cardiac hypertrophy. The present study aimed to investigate whether fibrinogen will stimulate the hypertrophic response of cardiac myocytes and to examine the role of the TLR4/MyD88/NF-κB pathway in fibrinogen-induced cardiac hypertrophy. Methods and Results Cardiac hypertrophy was induced by transverse aortic banding for 5 weeks in Sprague-Dawley rats. The deposition of fibrinogen in the left ventricle, as determined by immunohistochemistry and immunoblotting, was increased. Aortic banding also significantly enhanced the association of TLR4 with MyD88 and increased NF-κB activity. In-vitro studies showed that fibrinogen induced a dose-dependent, hypertrophic response of neonatal cardiomyocytes. Fibrinogen stimulation significantly increased myocyte size, 3H-leucine incorporation and mRNA levels of atrial natriuretic peptide (ANP); fibrinogen challenge also significantly increased associations of TLR4 with MyD88 and NF-κB binding activity. Transient transfection of cardiomyocytes with a dominant-negative MyD88 plasmid significantly attenuated the fibrinogen-induced hypertrophic response of neonatal cardiac myocytes and blunted fibrinogen-increased activation of the TLR4/MyD88/NF-κB signaling pathway. Conclusion Our results suggest that fibrinogen induces hypertrophic response of cardiomyocytes partially through a TLR4-mediated, MyD88-dependent NF-κB pathway.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-18408 |
| Date | 01 January 2009 |
| Creators | Li, Ting, Wang, Yongmei, Liu, Chunyang, Hu, Yulong, Wu, Meiling, Li, Jing, Guo, Lin, Chen, Liang, Chen, Qi, Ha, Tuanzhu, Li, Chuanfu, Li, Yuehua |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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