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Antibodies against electronegative LDL inhibit atherosclerosis in LDLr-/- mice
- Source :
- Brazilian Journal of Medical and Biological Research, Volume: 41, Issue: 12, Pages: 1086-1092, Published: DEC 2008, Brazilian Journal of Medical and Biological Research, Vol 41, Iss 12, Pp 1086-1092 (2008), Brazilian Journal of Medical and Biological Research v.41 n.12 2008, Brazilian Journal of Medical and Biological Research, Associação Brasileira de Divulgação Científica (ABDC), instacron:ABDC
- Publication Year :
- 2008
-
Abstract
- In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(-) on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/-) mice (6 per group) were immunized with the following antibodies (100 microg each): mouse anti-LDL(-) monoclonal IgG2b, rabbit anti-LDL(-) polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25% cholesterol) and then every week for 21 days. The passive immunization with anti-LDL(-) monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 +/- 9.7, 67.3 +/- 17.02, 56.9 +/- 8.02 microm(2) (mean +/- SD), respectively) compared to control (124.9 +/- 13.2 microm(2)). Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(-) monoclonal antibody (3.5 +/- 0.70 per field x 10) compared to controls (21.5 +/- 3.5 per field x 10). Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(-) in blood plasma (immunized: 1.0 +/- 1.4; control: 20.5 +/- 3.5 RLU), the amount of cholesterol oxides in plasma (immunized: 4.7 +/- 2.7; control: 15.0 +/- 2.0 pg COx/mg cholesterol) and liver (immunized: 2.3 +/- 1.5; control: 30.0 +/- 26.0 pg COx/mg cholesterol), and the hepatic content of lipid hydroperoxides (immunized: 0.30 +/- 0.020; control: 0.38 +/- 0.15 ng/mg protein). In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.
- Subjects :
- Physiology
Biochemistry
chemistry.chemical_compound
Mice
Blood plasma
General Pharmacology, Toxicology and Pharmaceutics
lcsh:QH301-705.5
lcsh:R5-920
biology
Chemistry
General Neuroscience
Antibodies, Monoclonal
General Medicine
Atherogenesis
Immunohistochemistry
Lipoproteins, LDL
Minimally modified LDL
lipids (amino acids, peptides, and proteins)
Female
Rabbits
Antibody
lcsh:Medicine (General)
Monoclonal antibody
medicine.medical_specialty
medicine.drug_class
Immunology
Biophysics
Vascular Cell Adhesion Molecule-1
Immunoglobulin Fab Fragments
Internal medicine
medicine
Animals
Cholesterol
Passive immunization
Immunization, Passive
Cell Biology
Atherosclerosis
Mice, Inbred C57BL
Endocrinology
lcsh:Biology (General)
Receptors, LDL
Polyclonal antibodies
Immunoglobulin G
LDL receptor
biology.protein
Lipid Peroxidation
Lipoprotein
Subjects
Details
- ISSN :
- 1414431X
- Volume :
- 41
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
- Accession number :
- edsair.doi.dedup.....238518870f39ad43be73409087224298