Activation of the innate immune system represents a vital step in inflammation during
cardiac remodeling induced by the angiotensin II (Ang II). This study aimed to explore
the role of Toll-like receptors 2 (TLR2) in Ang II-induced cardiac remodeling. We
investigated the effect of TLR2 deficiency on Ang II-induced cardiac remodeling by
utilizing TLR2 knockout mice, bone marrow transplantation models, and H9C2 cells.
Though TLR2 deficiency had no effect on body weight change, cardiac Ang II content
and blood pressure, it significantly ameliorated cardiac hypertrophy, fibrosis and
inflammation, as well as improved heart function. Further bone marrow transplantation
studies showed that TLR2-deficiency in cardiac cells but not bone marrow-derived cells
prevented Ang II-induced cardiac remodeling and cardiac dysfunction. The underlying
mechanism may involve increased TLR2-MyD88 interaction. Further in vitro studies in
Ang II-treated H9C2 cells showed that TLR2 knockdown by siRNA significantly decreased
Ang II-induced cell hypertrophy, fibrosis and inflammation. Moreover, Ang II significantly
increased TLR2-MyD88 interaction in H9C2 cells in a TLR4-independent manner. TLR2
deficiency in cardiac cells prevents Ang II-induced cardiac remodeling, inflammation
and dysfunction through reducing the formation of TLR2-MyD88 complexes. Inhibition
of TLR2 pathway may be a therapeutic strategy of hypertensive heart failure.
Abbreviations:
Ang II (angiotensin II), BM (bone marrow), CD31/ PECAM-1 (Platelet endothelial cell adhesion molecule-1), COL-I (collagen I), DMSO (dimethyl sulfoxide), GAPDH (glyceraldehyde 3-phosphate dehydrogenase), HF (heart failure), IL-1β (interleukin1β), β-MyHC (beta myosin heavy chain), NC (negative control), NF-κB (nuclear factor-κB), RAAS (renin-angiotensin-aldosterone system), RAS (renin-angiotensin system), TGF-β (transforming growth factor-β), TLR (toll-like receptor), TNF-α (tumor necrosis factor-α), Val (Valsartan)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 27, 2021
Accepted:
February 23,
2021
Received in revised form:
February 5,
2021
Received:
November 4,
2020
Identification
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