Genetic-dietary regulation of serum paraoxonase expression and its role in atherogenesis in a mouse model
| Autor: | Y R Xia, A M Fogelman, Aldon J. Lusis, Diana M. Shih, Susan Hama, L Gu, M Navab |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
DNA Complementary Arteriosclerosis Molecular Sequence Data Gene Expression Biology law.invention Mice chemistry.chemical_compound Species Specificity Inbred strain law Internal medicine Gene expression medicine Animals Humans Amino Acid Sequence RNA Messenger Cloning Molecular Diet Fat-Restricted Crosses Genetic Mice Inbred C3H Base Sequence Aryldialkylphosphatase Cholesterol Fatty streak Esterases Paraoxonase General Medicine medicine.disease Diet Lipoproteins LDL Mice Inbred C57BL Disease Models Animal Endocrinology Biochemistry chemistry Recombinant DNA biology.protein Diet Atherogenic Female lipids (amino acids peptides and proteins) Rabbits Lipoproteins HDL Oxidation-Reduction Research Article |
| Zdroj: | Journal of Clinical Investigation. 97:1630-1639 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci118589 |
| Popis: | In an effort to identify genetic factors contributing to atherogenesis, we have studied inbred strains of mice that are susceptible (C57BL/6J) and resistant (C3H/HeJ) to diet-induced aortic fatty streak lesions. When maintained on a low-fat diet, HDL isolated from both strain C57BL/6J (B6) and C3H/HeJ (C3H) mice protect against LDL oxidation in a coculture model of the artery wall. However, when maintained on an atherogenic diet high in fat and cholesterol, the HDL isolated from B6 mice lose the capacity to protect, whereas HDL from C3H mice protect equally well. Associated with the loss in the ability of HDL to protect is a decrease in the activity of serum paraoxonase, a serum esterase carried on HDL that has previously been shown to protect against LDL oxidation in vitro. The levels of paraoxonase mRNA decreased in B6 mice upon challenge with the atherogenic diet but increased in C3H, indicating that paraoxonase production is under genetic control. In a set of recombinant inbred strains derived from the B6 and C3H parental strains, low paraoxonase mRNA levels segregated with aortic lesion development, supporting a role for paraoxonase in atherogenesis. |
| Databáze: | OpenAIRE |
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