Fibrinogen Regulates Cardiac Hypertrophy Through MyD88-dependent NF-κB Signaling Pathway

Fibrinogen is an abundant blood coagulation factor which mainlysecrected by hepatic cell. Its plasma level has been correlated with manycardiovascular diseases (CVD) and has been defined as an important riskfactor for CVD such as cardiac hypertrophy and myocardial infarction:Fibrinogen participates in many diseases including mediatingleukocytes,platelet adhesion, endothelial cell proliferation, smoothmuscle cell proliferation, and tissue healing. The relationship betweenfibrinogen and cardiac hypertrophy is poorly understood. Our study is todetermine whether fibrinogen regulates the pathophysiologic process ofcardiac hypertrophy due to pressure overloaded.In our research we performed SD rats which underwentpressure-overload following transverse aorta constriction. We analyzedfibrinogen localization and expression in heart tissue. Moreover westudied whether fibrinogen can stimulate neonatal myocyte hypertrophyand the involving signaling pathway.After that time, a significant increase in heart weight especially leftventricle was observed. Myocyte surface area which analyzed byMasson's staining was increased along with microvascular fibrosis. Fibrinogen accumulation in left ventricle was increased (P＜0.05) whichmainly located in the extracellular matrix (ECM) compared with shamoperated group. Association of TLR4 and MyD88 was increased by20％(P＜0.05) as well as enhanced NF-κB binding activity (18％, P＜0.05)compared with sham operated group. P38 MAPK also activated andincreased by 220％(P＜0.05). Fibrinogen caused hypertrophic response inneonatal myocyte in a dose dependent manner by immunohistochemistryin vitro. Myocyte surface area was increased by 30％(P＜0.05) comparedwith control group, ANP mRNA level in banding group which is aspecific marker for myocytes hypertrophy was increased by 115％(P＜0.05) compared with control group. Synthesis of myocytes specificcytoskeietonα-actinin also increased. Nuclear factor-κB(NF-κB) bindingactivity was also enhanced by 69％(P＜0.05) through EMSA afterstimulation compared with control group. Transfection of dominantnegative MyD88 (dnMyD88) plasmid decreased these responses in vitro.From these studies we concluded fibrinogen correlated withpressure-overload induced cardiac hypertrophy and regulated neonatalmyocytes hypertrophy through MyD88-dependent NF-κB signalingpathway.