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Toll-like receptor 2-deficiency on bone marrow-derived cells augments vascular healing of murine arterial lesions.
- Source :
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Life sciences [Life Sci] 2020 Feb 01; Vol. 242, pp. 117189. Date of Electronic Publication: 2019 Dec 28. - Publication Year :
- 2020
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Abstract
- Aims: Neointimal hyperplasia contributes to arterial restenosis after percutaneous transluminal coronary angioplasty or vascular surgery. Neointimal thickening after arterial injury is determined by inflammatory processes. We investigated the role of the innate immune receptor toll-like receptor 2 (TLR2) in neointima formation after arterial injury in mice.<br />Materials and Methods: Carotid artery injury was induced by 10% ferric chloride in C57Bl/6J wild type (WT), TLR2 deficient (B6.129-Tlr2 <superscript>tm1Kir</superscript> /J, TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> ) and WT mice treated with a TLR2 blocking antibody. 21 days after injury, carotid arteries were assessed histomorphometrically and for smooth muscle cell (SMC) content. To identify the contribution of circulating cells in mediating the effects of TLR2-deficiency, arterial injury was induced in WT/TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> -chimeric mice and the paracrine modulation of bone marrow-derived cells from WT and TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> on SMC migration compared in vitro.<br />Key Findings: TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> mice and WT mice treated with TLR2 blocking antibodies exhibited reduced neointimal thickening (23.7 ± 4.2 and 6.5 ± 3.0 vs. 43.1 ± 5.9 μm, P < 0.05 and P < 0.01), neointimal area (5491 ± 1152 and 315 ± 76.7 vs. 13,756 ± 2627 μm <superscript>2</superscript> , P < 0.05 and P < 0.01) and less luminal stenosis compared to WT mice (8.5 ± 1.6 and 5.0 ± 1.3 vs. 22.4 ± 2.2%, both P < 0.001n = 4-8 mice/group). The phenotypes of TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> vs. WT mice were completely reverted in WT/TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> bone marrow chimeric mice (5.9 ± 1.5 μm neointimal thickness, 874.2 ± 290.2 μm <superscript>2</superscript> neointima area and 2.7 ± 0.6% luminal stenoses in WT mice transplanted with TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> bone marrow vs. 23.6 ± 5.1 μm, 3555 ± 511 μm <superscript>2</superscript> and 12.0 ± 1.3% in WT mice receiving WT bone marrow, all P < 0.05, n = 6/group). Neointimal lesions of WT and WT mice transplanted with TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> bone marrow chimeric mice showed increased numbers of SMC (10.8 ± 1.4 and 12.6 ± 1.4 vs. 3.8 ± 0.9 in TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> and 3.5 ± 1.1 cells in WT mice transplanted with TLR2 <superscript>-</superscript> <superscript>/</superscript> <superscript>-</superscript> bone marrow, all P < 0.05, n = 6). WT bone marrow cells stimulated SMC migration more than TLR2-deficient bone marrow cells (1.7 ± 0.05 vs. 1.3 ± 0.06-fold, P < 0.05, n = 7) and this effect was aggravated by TLR2 stimulation and diminished by TLR2 blockade (1.1 ± 0.03-fold after stimulation with TLR2 agonists and 0.8 ± 0.02-fold after TLR2 blockade vs. control treated cells defined as 1.0, P < 0.05, n = 7).<br />Significance: TLR2-deficiency on hematopoietic but not vessel wall resident cells augments vascular healing after arterial injury. Pharmacological blockade of TLR2 may thus be a promising therapeutic option to improve vessel patency after iatrogenic arterial injury.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Arteries injuries
Bone Marrow Transplantation
Carotid Artery Injuries metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle, Smooth, Vascular injuries
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular pathology
Neointima metabolism
Neointima pathology
Toll-Like Receptor 2 metabolism
Bone Marrow Cells metabolism
Toll-Like Receptor 2 deficiency
Wound Healing
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 242
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31891724
- Full Text :
- https://doi.org/10.1016/j.lfs.2019.117189