Intrinsic cardiac adrenergic (ICA) cells contribute to LPS-induced myocardial dysfunction

The role of ICA cells in septic cardiomyopathy is unknown. Here we show that norepinephrine (NE) secretion from ICA cells is increased through activation of Toll-like receptor 4 (TLR4) to aggravate myocardial TNF-a production and dysfunction by lipopolysaccharide (LPS). In ICA cells, LPS activated TLR4-MyD88/TRIF-AP-1 signaling that promoted NE biosynthesis through expression of tyrosine hydroxylase, but did not trigger TNF-a production due to impairment of p65 translocation. Our findings suggest that ICA cells may be a potential therapeutic target for septic cardiomyopathy. Overall design: To further clarify the role of ICA cells in LPS-induced cardiac TNF-a and compare the differentiall expressed genes between control and LPS-treated ICA cells