Publication

Toll-like receptor 7 deficiency promotes survival and reduces adverse left ventricular remodelling after myocardial infarction

de Kleijn, D. P. V., Chong, S. Y., Wang, X., Yatim, S. M. J. M., Fairhurst, A-M., Vernooij, F., Zharkova, O., Chan, M. Y., Foo, R. S. Y., Timmers, L., Lam, C. S. P. & Wang, J-W., 1-Oct-2019, In : Cardiovascular Research. 115, 12, p. 1791-1803 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

Copy link to clipboard

Documents

  • Toll-like receptor 7 deficiency promotes survival and reduces adverse left ventricular remodelling after myocardial infarction

    Final publisher's version, 2 MB, PDF document

    Request copy

DOI

  • Dominique P. V. de Kleijn
  • Suet Yen Chong
  • Xiaoyuan Wang
  • Siti Maryam J. M. Yatim
  • Anna-Marie Fairhurst
  • Flora Vernooij
  • Olga Zharkova
  • Mark Y. Chan
  • Roger S. Y. Foo
  • Leo Timmers
  • Carolyn S. P. Lam
  • Jiong-Wei Wang

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.

Original languageEnglish
Pages (from-to)1791-1803
Number of pages13
JournalCardiovascular Research
Volume115
Issue number12
Publication statusPublished - 1-Oct-2019

    Keywords

  • TLR7, Myocardial infarction, Inflammation, Fibrosis, Left ventricular remodelling, PREVENTS CARDIAC RUPTURE, SYSTEMIC-LUPUS-ERYTHEMATOSUS, CARDIOVASCULAR-DISEASE, EXTRACELLULAR-MATRIX, HEART, MICE, RNA, INFLAMMATION, MODEL, DYSFUNCTION

ID: 101942158