Key result
TLR7 deficiency in mice reduced acute cardiac rupture, decreased inflammatory cell influx, and resulted in less chronic adverse left ventricular remodelling and better cardiac function post-MI.
Why the study?
Because innate immune activation is involved in the response to myocardial infarction, this study aimed to determine if Toll-like receptor 7 contributes to post-MI ischaemic injury and adverse remodelling.
Does TLR7 deficiency reduce adverse left ventricular remodelling and improve cardiac function after myocardial infarction?
Does TLR7 deficiency reduce adverse left ventricular remodelling and improve cardiac function after myocardial infarction?
TLR7 deficiency protects against adverse left ventricular remodeling and improves cardiac function after myocardial infarction by modulating scar formation and inflammatory infiltration.
Answers are grounded in this paper and cite their sources.
TLR7 inhibition may reduce post-MI remodelling; extends preclinical evidence for innate immune targeting after infarction.
AIMS: The Toll-like receptor 7 (TLR7) is an intracellular innate immune receptor activated by nucleic acids shed from dying cells leading to activation of the innate immune system. Since innate immune system activation is involved in the response to myocardial infarction (MI), this study aims to identify if TLR7 is involved in post-MI ischaemic injury and adverse remodelling after MI. METHODS AND RESULTS: TLR7 involvement in MI was investigated in human tissue from patients with ischaemic heart failure, as well as in a mouse model of permanent left anterior descending artery occlusion in C57BL/6J wild type and TLR7 deficient (TLR7-/-) mice. TLR7 expression was up-regulated in human and mouse ischaemic myocardium after MI. Compared to wild type mice, TLR7-/- mice had less acute cardiac rupture associated with blunted activation of matrix metalloproteinase 2, increased expression of tissue inhibitor of metalloproteinase 1, recruitment of more myofibroblasts, and the formation of a myocardial scar with higher collagen fibre density. Furthermore, inflammatory cell influx and inflammatory cytokine expression post-MI were reduced in the TLR7-/- heart. During a 28-day follow-up after MI, TLR7 deficiency resulted in less chronic adverse left ventricular remodelling and better cardiac function. Bone marrow (BM) transplantation experiments showed that TLR7 deficiency in BM-derived cells preserved cardiac function after MI. CONCLUSIONS: In acute MI, TLR7 mediates the response to acute cardiac injury and chronic remodelling probably via modulation of post-MI scar formation and BM-derived inflammatory infiltration of the myocardium.
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Kleijn et al. (2019) studied Myocardial infarction and ischaemic heart failure. TLR7 deficiency vs. Wild type (TLR7 intact) was evaluated on Post-MI ischaemic injury and adverse remodelling (acute cardiac rupture, scar formation, inflammatory cell influx, cardiac function). TLR7 deficiency in mice reduced acute cardiac rupture, decreased inflammatory cell influx, and resulted in less chronic adverse left ventricular remodelling and better cardiac function post-MI.
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