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Editorial
. 2019 Oct 1;115(12):1687-1689.
doi: 10.1093/cvr/cvz128.

How do endosomal Toll-like receptors sense and extend ischaemic myocardial injury?

Nikolaos G Frangogiannis  1
Affiliations
Editorial

How do endosomal Toll-like receptors sense and extend ischaemic myocardial injury?

Nikolaos G Frangogiannis. Cardiovasc Res. .
No abstract available

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Figures

Figure 1
Figure 1
The role of the endosomal Toll-like receptor 7 (TLR7) in remodelling of the infarcted heart. The study by De Kleijn et al. suggests that endosomal TLR7 may be activated in infarct leucocytes, presumably by single-stranded RNA (ssRNA) released by dying cardiomyocytes, accentuating the immune response and promoting extracellular matrix degradation through release of matrix metalloproteinases (MMPs). Several important questions remain to be answered: (i) How does ssRNA find its way to leucocyte endosomes to activate TLR7? Receptor-mediated endocytosis and autophagic pathways may be implicated. Moreover, release of high-mobility group box protein 1 (HMGB1) following infarction may prime ssRNA for endocytosis. (ii) Which cells exhibit TLR7 activation? TLR7 is constitutively expressed by dendritic cells and B lymphocytes and is markedly induced following inflammation in macrophages and in non-immune cell types. (iii) Which downstream signals mediate the effects of TLR7 in the infarcted heart? Following interaction with ssRNA in endosomes, TLR7 dimerizes and may activate nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) through a myeloid differentiation primary response protein 88 (MyD88)-dependent pathway, thus inducing synthesis of cytokines and chemokines. TLR7-mediated MMP secretion may also play a role in mediating cardiac rupture and adverse remodelling of the infarcted heart. Additional symbols: IL, interleukin; TNF, tumour necrosis factor; IRAK, interleukin-1 receptor-associated kinase.
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