An animal model to study local oxidation of LDL and its biological effects in the arterial wall.
Oxidized LDL (oxLDL) is present in atherosclerotic lesions and is believed to play a key role in atherogenesis. Mainly on the basis of cell culture studies, oxLDL has been shown to produce many biological effects that influence the atherosclerotic process. To study LDL oxidation in vivo, we have established a model in which Sprague-Dawley rats are given a single injection of unmodified human LDL (> or = 4 mg/kg body weight). Within 6 hours, an accumulation of apolipoprotein B and epitopes present on oxLDL are detected in the arterial endothelium and media. The presence of oxLDL is associated with activation of the transcription factor nuclear factor-kappaB in the endothelium as well as endothelial expression of intercellular adhesion molecule-1. Injection of LDL enriched with the antioxidant probucol resulted in arterial accumulation of apolipoprotein B, but the expression of oxLDL-specific epitopes was reduced at 24 hours. Thus, this simple model has the potential to analyze the mechanisms behind and biological effects of LDL oxidation in vivo.
Calara
F
F
King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden. rcalara@instmed.ks.se
Dimayuga
P
P
Niemann
A
A
Thyberg
J
J
Diczfalusy
U
U
Witztum
J L
JL
Palinski
W
W
Shah
P K
PK
Cercek
B
B
Nilsson
J
J
Regnström
J
J
D000328:Adult; D000818:Animals; D001158:Arteries / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D008077:Lipoproteins, LDL; D016328:NF-kappa B; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1