Novel cerebrovascular pathology in mice fed a high cholesterol diet
| Autor: | Miguel A. Gama Sosa, Sam Gandy, Dara L. Dickstein, Patrick R. Hof, Elizabeth Oler, Joseph D. Buxbaum, Sonia Franciosi, James Schmeidler, Gregory A. Elder, Christoph Schmitz, Rita De Gasperi, William G.M. Janssen, Twethida Oung, Daniel F. English |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Apolipoprotein E
Pathology medicine.medical_specialty Central nervous system Clinical Neurology lcsh:Geriatrics lcsh:RC346-429 High cholesterol Cellular and Molecular Neuroscience chemistry.chemical_compound medicine Molecular Biology Microvessel lcsh:Neurology. Diseases of the nervous system Cholesterol business.industry Microvascular Density medicine.disease lcsh:RC952-954.6 medicine.anatomical_structure chemistry LDL receptor lipids (amino acids peptides and proteins) Neurology (clinical) business Lipoprotein Research Article |
| Zdroj: | Molecular Neurodegeneration Molecular Neurodegeneration, Vol 4, Iss 1, p 42 (2009) |
| ISSN: | 1750-1326 |
| Popis: | Background Hypercholesterolemia causes atherosclerosis in medium to large sized arteries. Cholesterol is less known for affecting the microvasculature and has not been previously reported to induce microvascular pathology in the central nervous system (CNS). Results Mice with a null mutation in the low-density lipoprotein receptor (LDLR) gene as well as C57BL/6J mice fed a high cholesterol diet developed a distinct microvascular pathology in the CNS that differs from cholesterol-induced atherosclerotic disease. Microvessel diameter was increased but microvascular density and length were not consistently affected. Degenerative changes and thickened vascular basement membranes were present ultrastructurally. The observed pathology shares features with the microvascular pathology of Alzheimer's disease (AD), including the presence of string-like vessels. Brain apolipoprotein E levels which have been previously found to be elevated in LDLR-/- mice were also increased in C57BL/6J mice fed a high cholesterol diet. Conclusion In addition to its effects as an inducer of atherosclerosis in medium to large sized arteries, hypercholesterolemia also induces a microvascular pathology in the CNS that shares features of the vascular pathology found in AD. These observations suggest that high cholesterol may induce microvascular disease in a range of CNS disorders including AD. |
| Databáze: | OpenAIRE |
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