Effects of 3-deazaadenosine on homocysteine and atherosclerosis in apolipoprotein E-deficient mice

Objective: In the past decade, elevated homocysteine concentration has achieved widespread recognition as an independent risk factor in the development of atherosclerosis. 3-Deazaadenosine (c 3Ado) is a potent inhibitor and substrate for S-adenosylhomocysteine hydrolase and therefore may reduce homo...

Full description

Saved in:
Bibliographic Details
Published in:Atherosclerosis 2003-12, Vol.171 (2), p.181-192
Main Authors: Langheinrich, Alexander Claus, Braun-Dullaeus, Ruediger Christian, Walker, Gerhard, Jeide, Ina, Schilling, Ralph, Tammoscheit, Kai, Dreyer, Thomas, Fink, Ludger, Bohle, Rainer Maria, Haberbosch, Werner
Format: Article
Language:English
Subjects:
Adenosine analogues
Analysis of Variance
Animals
Apolipoproteins E - deficiency
Arteriosclerosis - drug therapy
Arteriosclerosis - pathology
Atherosclerosis
Atherosclerosis (general aspects, experimental research)
Base Sequence
Biological and medical sciences
Biopsy, Needle
Blood and lymphatic vessels
Cardiology. Vascular system
Cell adhesion molecules
Cholesterol - metabolism
Diet, Atherogenic
Disease Models, Animal
DNA, Complementary - analysis
Flow Cytometry
Homocysteine
Homocysteine - drug effects
Homocysteine - metabolism
Immunohistochemistry
Male
Medical sciences
Methylation
Mice
Mice, Knockout
Molecular Sequence Data
Polymerase Chain Reaction
Probability
Reference Values
RNA, Messenger - analysis
Sinus of Valsalva - drug effects
Sinus of Valsalva - pathology
Transaminases - metabolism
Tubercidin - pharmacology
Tunica Intima - drug effects
Tunica Intima - pathology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objective: In the past decade, elevated homocysteine concentration has achieved widespread recognition as an independent risk factor in the development of atherosclerosis. 3-Deazaadenosine (c 3Ado) is a potent inhibitor and substrate for S-adenosylhomocysteine hydrolase and therefore may reduce homocysteine concentrations. The current study investigated the effect of c 3Ado on serum homocysteine, atherosclerotic lesions, and the expression of adhesion molecules in apoE-knockout mice. Methods and results: Animals were placed on an atherogenic diet with or without c 3Ado for 12 and 24 weeks. Frozen cross-sections of the aortic sinus and the proximal aorta were analyzed by computer-aided planimetry for fatty plaque formation. Macrophages, VCAM-1 and ICAM-1 were quantified by immunhistochemistry and oligo-cell reverse transcription polymerase chain reaction after laser microdissection. Application of c 3Ado resulted in significant reduction of homocysteine levels by 35.9 and 45.3% after 12 and 24 weeks, respectively ( P
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2003.08.028