Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Willecke, F; Rupprecht, B; Gissler, MC; Pfeiffer, K; Anto-Michel, N; Stachon, P; Wolf, D; Hilgendorf, I; Hoppe, N; Bode, C; Zirlik, A.
Tumor Necrosis Factor Receptor-Associated Factor 5 Promotes Arterial Neointima Formation through Smooth Muscle Cell Proliferation.
J Vasc Res. 2019; 56(6):308-319
Doi: 10.1159/000501615
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Anto Michel Nathaly
- Zirlik Andreas
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- Abstract:
- Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are cytoplasmic adaptor proteins of the TNF/interleukin (IL)-1/Toll-like receptor superfamily. Ligands of this family such as TNFα, CD40L, and IL-1β promote chronic inflammatory processes such as atherosclerosis and restenosis, the latter being a common adverse reaction after vascular interventions. We previously reported overexpression of TRAF5 in murine and human atheromata and TRAF5-dependent proinflammatory functions in vitro. However, the role of TRAF5 in restenosis remains unsettled. To evaluate whether TRAF5 affects neointima formation, TRAF5-/-LDLR-/- and TRAF5+/+LDLR-/- mice consuming a high cholesterol diet (HCD) received wire-induced injury of the carotid artery. After 28 days, TRAF5-deficient mice showed a 45% decrease in neointimal area formation compared with TRAF5-compentent mice. Furthermore, neointimal vascular smooth muscle cells (vSMC) and macrophages decreased whereas collagen increased in TRAF5-deficient mice. Mechanistically, the latter expressed lower transcript levels of the matrix metalloproteinases 2 and 9, both instrumental in extracellular matrix degradation and vSMC mobilization. Additionally, TRAF5-specific siRNA interference rendered murine vSMC less proliferative upon CD40L stimulation. In accordance with these findings, fewer vSMC isolated from TRAF5-deficient aortas were in a proliferative state as assessed by Ki67 and cyclin B1 expression. In conclusion, TRAF5 deficiency mitigates neointima formation in mice, likely through a TRAF5-dependent decrease in vSMC proliferation. © 2019 S. Karger AG, Basel.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- CD40 Antigens - metabolism
- Carotid Arteries - metabolism
- Carotid Arteries - pathology
- Carotid Artery Diseases - genetics
- Carotid Artery Diseases - metabolism
- Carotid Artery Diseases - pathology
- Cell Proliferation -
- Cholesterol, Dietary -
- Disease Models, Animal -
- Macrophages - metabolism
- Macrophages - pathology
- Male -
- Matrix Metalloproteinase 2 - metabolism
- Matrix Metalloproteinase 9 - metabolism
- Mice, Inbred C57BL -
- Mice, Knockout -
- Muscle, Smooth, Vascular - metabolism
- Muscle, Smooth, Vascular - pathology
- Myocytes, Smooth Muscle - metabolism
- Myocytes, Smooth Muscle - pathology
- Neointima -
- Plaque, Atherosclerotic -
- Receptors, LDL - genetics
- Receptors, LDL - metabolism
- Signal Transduction -
- TNF Receptor-Associated Factor 5 - deficiency
- TNF Receptor-Associated Factor 5 - genetics
- TNF Receptor-Associated Factor 5 - metabolism
- Find related publications in this database (Keywords)
- Restenosis
- Neointima
- Vascular smooth muscle cells
- Inflammation
- TRAF5
- Tumor necrosis factor