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Microbiota control acute arterial inflammation and neointimal hyperplasia development after arterial injury
- Source :
- PLoS ONE, Vol 13, Iss 12, p e0208426 (2018), PLoS ONE
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- BackgroundThe microbiome has a functional role in a number of inflammatory processes and disease states. While neointimal hyperplasia development has been linked to inflammation, a direct role of the microbiota in neointimal hyperplasia has not yet been established. Germ-free (GF) mice are an invaluable model for studying causative links between commensal organisms and the host. We hypothesized that GF mice would exhibit altered neointimal hyperplasia following carotid ligation compared to conventionally raised (CONV-R) mice.MethodsTwenty-week-old male C57BL/6 GF mice underwent left carotid ligation under sterile conditions. Maintenance of sterility was assessed by cultivation and 16S rRNA qPCR of stool. Neointimal hyperplasia was assessed by morphometric and histologic analysis of arterial sections after 28 days. Local arterial cell proliferation and inflammation was assessed by immunofluorescence for Ki67 and inflammatory cell markers at five days. Systemic inflammation was assessed by multiplex immunoassays of serum. CONV-R mice treated in the same manner served as the control cohort. GF and CONV-R mice were compared using standard statistical methods.ResultsAll GF mice remained sterile during the entire study period. Twenty-eight days after carotid ligation, CONV-R mice had significantly more neointimal hyperplasia development compared to GF mice, as assessed by intima area, media area, intima+media area, and intima area/(intima+media) area. The collagen content of the neointimal lesions appeared qualitatively similar on Masson's trichrome staining. There was significantly reduced Ki67 immunoreactivity in the media and adventitia of GF carotid arteries 5 days after ligation. GF mice also had increased arterial infiltration of anti-inflammatory M2 macrophages compared to CONV-R mouse arteries and a reduced proportion of mature neutrophils. GF mice had significantly reduced serum IFN-γ-inducible protein (IP)-10 and MIP-2 5 days after carotid ligation, suggesting a reduced systemic inflammatory response.ConclusionsGF mice have attenuated neointimal hyperplasia development compared to CONV-R mice, which is likely related to altered kinetics of wound healing and acute inflammation. Recognizing the role of commensals in the regulation of arterial remodeling will provide a deeper understanding of the pathophysiology of restenosis and support strategies to treat or reduce restenosis risk by manipulating microbiota.
- Subjects :
- Male
0301 basic medicine
Pathology
Neutrophils
Physiology
Pathology and Laboratory Medicine
Systemic inflammation
Mice
White Blood Cells
Restenosis
Animal Cells
RNA, Ribosomal, 16S
Immune Physiology
Medicine and Health Sciences
Immune Response
Neointimal hyperplasia
Innate Immune System
Multidisciplinary
Microbiota
Chemotaxis
Arteries
Genomics
Animal Models
Hyperplasia
3. Good health
Cell Motility
Carotid Arteries
medicine.anatomical_structure
Experimental Organism Systems
Medical Microbiology
Cytokines
Medicine
Anatomy
Cellular Types
Chemokines
medicine.symptom
Research Article
DNA, Bacterial
medicine.medical_specialty
Immune Cells
Science
Immunology
Mouse Models
Inflammation
Microbial Genomics
Research and Analysis Methods
DNA, Ribosomal
Microbiology
03 medical and health sciences
Signs and Symptoms
Model Organisms
Diagnostic Medicine
Neointima
Adventitia
Genetics
medicine
Animals
Germ-Free Life
Humans
Arteritis
Blood Cells
Bacteria
business.industry
Macrophages
Biology and Life Sciences
Cell Biology
Molecular Development
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
Ki-67 Antigen
030104 developmental biology
Immune System
Cardiovascular Anatomy
Animal Studies
Blood Vessels
Microbiome
Carotid Artery Injuries
Ligation
Wound healing
business
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 13
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....aa3af7fe36094aa1ac2f6d705f226b04