Cardiovascular research
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Cardiovascular research · Mar 2014
Inhibition of Toll-like receptor 2 reduces cardiac fibrosis by attenuating macrophage-mediated inflammation.
Toll-like receptor 2 (TLR2) is an important player in innate immunity, and recent studies have identified TLR2 as a critical mediator in cardiovascular diseases. Here, we investigated the involvement of TLR2 in angiotensin (Ang) II-induced cardiac fibrosis and the underlying mechanisms. ⋯ Inhibition of TLR2 protects against Ang II-induced cardiac fibrosis by attenuating macrophage recruitment and the inflammatory response in the heart and may be a novel potential therapeutic target for hypertensive heart disease.
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Cardiovascular research · Mar 2014
Thrombomodulin's lectin-like domain reduces myocardial damage by interfering with HMGB1-mediated TLR2 signalling.
Thrombomodulin (TM), via its lectin-like domain (LLD), exhibits anti-inflammatory properties partly by sequestering the pro-inflammatory cytokine, high-mobility group box 1 (HMGB1). Since myocardial damage after ischaemia and reperfusion is mediated by inflammation, we evaluated the cardioprotective effects of the LLD of TM. Using an in vivo mouse model of transient ischaemia and in vitro models of cardiomyocyte hypoxia, we assessed the ability of the LLD to suppress HMGB1-mediated activation of the receptors, receptor for advanced glycation endproducts (RAGEs) and Toll-like receptors (TLRs) 2 and 4. ⋯ The LLD of TM suppresses HMGB1-induced and TLR2-mediated myocardial reperfusion injury and apoptosis in vitro and in vivo.