MyD88-dependent nuclear factor-kappaB activation is involved in fibrinogen-induced hypertrophic response of cardiomyocytes.
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-kappaB (NF-kappaB) 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-kappaB pathway in fibrinogen-induced cardiac hypertrophy.


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-kappaB 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-kappaB 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-kappaB signaling pathway.


CONCLUSIONS
Our results suggest that fibrinogen induces hypertrophic response of cardiomyocytes partially through a TLR4-mediated, MyD88-dependent NF-kappaB pathway.
Li
Ting
T
Department of Pathophysiology, Nanjing Medical University, Jiangsu province, 210029, China.
Wang
Yongmei
Y
Liu
Chunyang
C
Hu
Yulong
Y
Wu
Meiling
M
Li
Jing
J
Guo
Lin
L
Chen
Liang
L
Chen
Qi
Q
Ha
Tuanzhu
T
Li
Chuanfu
C
Li
Yuehua
Y