RT Journal Article
ID 0c53ae6a549f3743
A1 Volz, Hans Christian 
A1 Schiekofer, Stephan 
A1 Kaya, Ziya 
A1 Katus, Hugo A. 
A1 Andrassy, Martin 
T1 RAGE and NF-κB Signaling in Heart Disease
JF Onco Therapeutics
JO OT
YR 2013
FD 2013-12-23
VO 4
IS 2
SP 133
OP 147
K1 innate immunity
K1 inflammatory heart disease
K1 myocarditis
K1 heart failure
K1 cardiomyopathy
K1 HMGB1
AB Advanced glycation end products (AGEs), S100/calgranulins, high-mobility group box (HMGB)1-protein, amyloid β-peptides, and the family of β-sheet fibrils have been shown to contribute to a number of chronic diseases such as diabetes, amyloidosis, and cancer by promoting cellular dysfunction via binding to the receptor for advanced glycation end products (RAGE). Engagement of RAGE leads to the activation of the nuclear factor (NF)-κB superfamily of transcription factors, which have been implicated in the regulation of numerous cellular processes such as cell survival, apoptosis, and secretion of cytokines in many cell types in immune cells but also cardiomyocytes, endothelial cells, and fibroblasts. However, sustained activation of NF-κB seems to be detrimental and promotes the development of heart failure by eliciting signals that trigger chronic inflammation through enhanced elaboration of various cytokines including tumour necrosis factor a (TNF-α), interleukin-1 (IL-1), and interleukin 6 (IL-6). Furthermore, engagement of RAGE appears to lead to prolonged NF-κB-mediated activation overwhelming endogenous autoregulatory feedback inhibition loops. The underlying mechanisms that account for the multifaceted and differential effects of NF-κB on cardiac cells are presently not fully understood. In this review, we will focus on the role of RAGE as a master switch of inflammation by converting a brief pulse of cellular activation to sustained cellular dysfunction. Furthermore, we discuss how duration of activation and cellular context may explain mechanistically the differential effects of NF-κB signaling in the heart.
PB Begell House
LK https://www.dl.begellhouse.com/journals/2c6306423483e001,1f0af71c0c22c607,0c53ae6a549f3743.html