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Deficiency of TLR4 homologue RP105 aggravates outward remodeling in a murine model of arteriovenous fistula failure
- Source :
- Scientific Reports, 7, Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017), Scientific Reports
- Publication Year :
- 2017
-
Abstract
- Arteriovenous access dysfunction is a major cause of morbidity for hemodialysis patients. The pathophysiology of arteriovenous fistula (AVF) maturation failure is associated with inflammation, impaired outward remodeling (OR) and intimal hyperplasia. RP105 is a critical physiologic regulator of TLR4 signaling in numerous cell types. In the present study, we investigated the impact of RP105 on AVF maturation, and defined cell-specific effects of RP105 on macrophages and vascular smooth muscle cells (VSMCs). Overall, RP105−/− mice displayed a 26% decrease in venous OR. The inflammatory response in RP105−/− mice was characterized by accumulation of anti-inflammatory macrophages, a 76% decrease in pro- inflammatory macrophages, a 70% reduction in T-cells and a 50% decrease in MMP-activity. In vitro, anti-inflammatory macrophages from RP105−/− mice displayed increased IL10 production, while MCP1 and IL6 levels secreted by pro-inflammatory macrophages were elevated. VSMC content in RP105−/− AVFs was markedly decreased. In vitro, RP105−/− venous VSMCs proliferation was 50% lower, whereas arterial VSMCs displayed a 50% decrease in migration, relative to WT. In conclusion, the impaired venous OR in RP105−/− mice could result from of a shift in both macrophages and VSMCs towards a regenerative phenotype, identifying a novel relationship between inflammation and VSMC function in AVF maturation.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Cell type
Intimal hyperplasia
Vascular smooth muscle
Biopsy
Myocytes, Smooth Muscle
Fluorescent Antibody Technique
lcsh:Medicine
Arteriovenous fistula
Inflammation
Vascular Remodeling
030204 cardiovascular system & hematology
Article
Muscle, Smooth, Vascular
Mice
03 medical and health sciences
0302 clinical medicine
Antigens, CD
Internal medicine
medicine
Animals
Humans
lcsh:Science
Cells, Cultured
Cell Proliferation
Mice, Knockout
Multidisciplinary
business.industry
Macrophages
lcsh:R
medicine.disease
Immunohistochemistry
Matrix Metalloproteinases
Pathophysiology
Disease Models, Animal
Interleukin 10
030104 developmental biology
Endocrinology
Arteriovenous Fistula
Immunology
TLR4
Cytokines
lcsh:Q
medicine.symptom
business
Biomarkers
Gene Deletion
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, 7, Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017), Scientific Reports
- Accession number :
- edsair.doi.dedup.....6306d60d8b76e923e52492cecd83d201