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CCR5 Deficiency Does Not Reduce Hypertensive End-Organ Damage in Mice.
MedLine Citation:
PMID:  22258337     Owner:  NLM     Status:  Publisher    
BackgroundCCR5 is expressed on infiltrating T cells in hypertensive mice and CCR5 antagonists reduce hypertension making CCR5 an interesting target in treatment of hypertension.MethodsTo evaluate the role of CCR5 in hypertensive renal and cardiac end-organ damage, we induced hypertension with desoxycorticosterone acetate (DOCA) and angiotensin II (Ang II) in wild-type (WT) and CCR5-deficient mice.ResultsCCR5 expression was increased in renal cortex and cardiac tissue as measured by quantitative PCR. Systolic blood pressure and renal function did not differ between hypertensive CCR5(-/-) and WT mice. DOCA + Ang II induced massive albuminuria and glomerular injury but no difference was found between CCR5(-/-) and WT mice. In addition, no difference was found for renal inflammation as measured by infiltrating T cells, macrophages, and CCL2 expression. The renal expression of the CCR5 ligands, CCL3, and CCL5 was increased in the kidney of hypertensive mice. For CCL3 the increase was significantly higher in CCR5(-/-) than in WT mice. DOCA + Ang II induced cardiac damage as assessed by heart weight, cardiac fibrosis as well as expression of fetal and matrix components but no significant difference was found between CCR5(-/-) and WT mice.ConclusionsCCR5 deficiency does not influence hypertensive renal and cardiac end-organ damage. Cells that infiltrate by expression of CCR5 are either not pathogenic or CCR5-positive leukocytes can migrate via alternative chemokine receptors. Beneficial effects of CCR5 antagonists in hypertension are most likely due to unspecific effects of the antagonists. Possibly, other chemokine receptors in concert with CCR5 are important for hypertensive injury.American Journal of Hypertension 2012; doi:10.1038/ajh.2011.243.
Christian Krebs; Christoph Fraune; Robin Schmidt-Haupt; Jan-Eric Turner; Ulf Panzer; Michael N Quang; Andrea Tannapfel; Joachim Velden; Rolf A Stahl; Ulrich O Wenzel
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-19
Journal Detail:
Title:  American journal of hypertension     Volume:  -     ISSN:  1941-7225     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Medicine, Division of Nephrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
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