Document Detail


Monoclonal antibody against marinobufagenin reverses cardiac fibrosis in rats with chronic renal failure.
MedLine Citation:
PMID:  22378033     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Cardiotonic steroids (CTS) are implicated in pathophysiology of uremic cardiomyopathy. In the present study, we tested whether a monoclonal antibody (mAb) against the bufadienolide CTS, marinobufagenin (MBG), alleviates cardiac hypertrophy and fibrosis in partially nephrectomized (PNx) rats.
METHODS: In PNx rats, we compared the effects of 3E9 anti-MBG mAb and of Digibind, an affinity-purified digoxin antibody, on blood pressure and cardiac hypertrophy and fibrosis following 4 weeks after the surgery.
RESULTS: In PNx rats, a fourfold elevation in plasma MBG levels was associated with hypertension, increased cardiac levels of carbonylated protein, cardiac hypertrophy, a reduction in cardiac expression of a nuclear transcription factor which is a negative regulator of collagen synthesis, Friend leukemia integration-1 (Fli-1), and an increase in the levels of collagen-1. A single intraperitoneal administration of 3E9 mAb to PNx rats reduced blood pressure by 59 mm Hg for 7 days and produced a significant reduction in cardiac weight and cardiac levels of oxidative stress, an increase in the expression of Fli-1, and a reduction in cardiac fibrosis. The effects of Digibind were similar to those of 3E9 mAb, but were less pronounced.
CONCLUSIONS: In experimental chronic renal failure, elevated levels of MBG contribute to hypertension and induce cardiac fibrosis via suppression of Fli-1, representing a potential target for therapy.
Authors:
Steven T Haller; David J Kennedy; Amjad Shidyak; George V Budny; Deepak Malhotra; Olga V Fedorova; Joseph I Shapiro; Alexei Y Bagrov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2012-03-01
Journal Detail:
Title:  American journal of hypertension     Volume:  25     ISSN:  1941-7225     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-17     Completed Date:  2012-10-23     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  690-6     Citation Subset:  IM    
Affiliation:
College of Medicine, University of Toledo, Toledo, Ohio, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / pharmacology,  therapeutic use*
Blood Pressure / drug effects,  physiology
Bufanolides / immunology*,  metabolism
Cardiomegaly / etiology*,  metabolism,  prevention & control*
Comorbidity
Disease Models, Animal
Fibrosis
Immunoglobulin Fab Fragments / pharmacology,  therapeutic use
Kidney Failure, Chronic / complications*,  metabolism,  surgery
Male
Myocardium / metabolism,  pathology*
Nephrectomy
Proto-Oncogene Protein c-fli-1 / metabolism
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
HL071556/HL/NHLBI NIH HHS; Z01 AG000869-01/AG/NIA NIH HHS; Z01 AG000869-02/AG/NIA NIH HHS; ZIA AG000869-02/AG/NIA NIH HHS; ZIA AG000869-03/AG/NIA NIH HHS; ZIA AG000869-04/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Bufanolides; 0/Immunoglobulin Fab Fragments; 0/Proto-Oncogene Protein c-fli-1; 0/digoxin antibodies Fab fragments; 470-42-8/marinobufagenin
Comments/Corrections

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