Atherogenesis in transgenic mice with human apolipoprotein B and lipoprotein (a)
| Autor: | Wulf Palinski, Rajendra K. Tangirala, M. J. Callow, J. Verstuyft, Edward M. Rubin |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
Apolipoprotein B Arteriosclerosis Inbred Strains Inbred C57BL MOUSE Apoprotein(a) Medical and Health Sciences Transgenic Muscle Smooth Vascular chemistry.chemical_compound Mice Reference Values Aorta biology General Medicine Lipoprotein(a) Muscle lipids (amino acids peptides and proteins) Female Smooth Research Article Genetically modified mouse medicine.medical_specialty LP(A) Transgene Immunology Mice Inbred Strains Mice Transgenic LDL medicine.artery Internal medicine Vascular medicine Animals Humans Apolipoproteins B Cholesterol Fatty streak Mice Inbred C57BL Endocrinology Apolipoproteins chemistry ATHEROSCLEROSIS biology.protein TRANSGENE Lipoprotein |
| Zdroj: | The Journal of clinical investigation, vol 96, iss 3 |
| ISSN: | 0021-9738 |
| Popis: | The engineering of mice that express a human apoB transgene has resulted in animals with high levels of human-like LDL particles and through crosses with human apo(a) transgenics, high levels of human-like lipoprotein (a) (Lp[a]) particles. In this study, these animals have been used to compare the atherogenic properties of apo(a), LDL, and Lp(a). The presence of the high expressing apoB (apoBH) transgene was associated with a 2.5-fold increase in VLDL-LDL cholesterol (primarily in the LDL fraction) and a 15-fold increase in proximal lesions compared with non-transgenic mice (P < or = 0.0001), while the presence of the low expressing human apoB (apoBL) transgene was not associated with major changes in lipoprotein profiles or increases in aortic lesion size. Examination of aortas of apoBH mice demonstrated lesions along the entire length of the aorta and immunochemical analysis of the lesions revealed features characteristically seen in human lesions including the presence of oxidized lipoproteins, macrophages, and immunoglobulins. Unlike animals with the apoBL transgene, animals with the apo(a) transgene had significant increases in proximal aortic fatty streak lesions compared to nontransgenic control animals (threefold; P < 0.02), while animals with both transgenes, the apo(a)/apo BL double transgenics, had lesions 2.5 times greater than animals expressing the apo(a) transgene alone and eightfold (P < 0.0006) greater than nontransgenic animals. These murine studies demonstrate that marked increases in apoB and LDL resulted in atherosclerotic lesions extending down the aorta which resemble human lesions immunochemically and suggest that apo(a) associated with apoB and lipid may result in a more pro-atherogenic state than when apo(a) is free in plasma. |
| Databáze: | OpenAIRE |
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