RGD Reference Report - Inhibition of chemokine receptor CCR2 and CCR5 expression contributes to simvastatin-induced attenuation of cardiac allograft vasculopathy. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Inhibition of chemokine receptor CCR2 and CCR5 expression contributes to simvastatin-induced attenuation of cardiac allograft vasculopathy.

Authors: Yin, R  Zhu, J  Shao, H  Cheng, X  Feng, X  Li, Z  Jing, H 
Citation: Yin R, etal., J Heart Lung Transplant. 2007 May;26(5):485-93.
RGD ID: 4890438
Pubmed: PMID:17449418   (View Abstract at PubMed)
DOI: DOI:10.1016/j.healun.2007.02.006   (Journal Full-text)

BACKGROUND: Accumulating evidence reveals that statins possess pleiotropic properties beyond cholesterol reduction, which may contribute to the attenuation of cardiac allograft vasculopathy (CAV). Recent in vitro data suggest that statins could down-regulate chemokine receptors. This study was designed to test the hypothesis that simvastatin ameliorates CAV development via the inhibition of chemokine receptor expression in an inbred rat model of cardiac transplantation. METHODS: Animals were divided into four groups: isograft; control (cyclosporine [CsA] + vehicle); low-dose simvastatin (LSIM; CsA + 5 mg/kg simvastatin); and high-dose simvastatin (HSIM; CsA + 10 mg/kg simvastatin). Donor hearts from Fisher 344 rats were transplanted heterotopically into Lewis rat recipients. CsA was administered at 1.5 mg/kg/day for 2 weeks post-operatively. In addition, recipients were treated daily with simvastatin or vehicle for 8 weeks. Donor hearts were harvested for histopathologic and immunohistochemical examination. Intragraft concentration of chemokines and chemokine receptor expression were analyzed using enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction, respectively. RESULTS: Both low and high doses of simvastatin significantly decreased the CAV score; inhibited recruitment of T lymphocytes and macrophages; reduced levels of intragraft MCP-1 (monocyte chemoattractant protein-1), RANTES (regulated on activation, normal T-cell expressed and secreted) protein and IP-10 (interferon-inducible protein-10); and down-regulated expression of chemokine receptors CCR2 and CCR5. CXCR3 expression was not affected by simvastatin treatment. CONCLUSIONS: Our results demonstrate that simvastatin may attenuate CAV development, possibly through retarding intragraft chemokine accumulation and chemokine receptor expression.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCR5Humancoronary artery disease  ISOCcr5 (Rattus norvegicus)mRNA:increased expression:heart (rat)RGD 
Ccr5Ratcoronary artery disease  IEP mRNA:increased expression:heart (rat)RGD 
Ccr5Mousecoronary artery disease  ISOCcr5 (Rattus norvegicus)mRNA:increased expression:heart (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Mus musculus)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Homo sapiens)
CCR5  (C-C motif chemokine receptor 5)


Additional Information