Advances in experimental dyslipidemia and atherosclerosis.
Among the models of dyslipidemia and atherosclerosis, a number of wild-type, naturally defective, and genetically modified animals (rabbits, mice, pigeons, dogs, pigs, and monkeys) have been characterized. In particular, their similarities to and differences from humans in respect to relevant biochemical, physiologic, and pathologic conditions have been evaluated. Features of atherosclerotic lesions and their specific relationship to plasma lipoprotein particles have been critically reviewed and summarized. All animal models studied have limitations: the most significant advantages and disadvantages of using a specific animal species are outlined here. New insights in lipid metabolism and genetic background with regard to variations in pathogenesis of dyslipidemia-associated atherogenesis have also been reviewed. Evidence suggests that among wild-type species, strains of White Carneau pigeons and Watanabe Heritable Hyperlipidemic and St. Thomas's Hospital rabbits are preferable to the cholesterol-fed wild-type animal species in dyslipidemia and atherosclerosis research. Evidence for the usefulness of both wild-type and transgenic animals in studying the involvement of inflammatory pathways and Chlamydia pneumoniae infection in pathogenesis of atherosclerosis has also been summarized. Transgenic mice and rabbits are excellent tools for studying specific gene-related disorders. However, despite these significant achievements in animal experimentation, there are no suitable animal models for several rare types of fatal dyslipidemia-associated disorders such as phytosterolemia and cerebrotendinous xanthomatosis. An excellent model of diabetic atherosclerosis is unavailable. The question of reversibility of atherosclerosis still remains unanswered. Further work is needed to overcome these deficiencies.
Moghadasian
M H
MH
Healthy Heart Program, Department of Pathology and Laboratory Medicine, St. Paul's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada. mhmoghad@interchange.ubc.ca
Frohlich
J J
JJ
McManus
B M
BM
D000818:Animals; D001161:Arteriosclerosis; D004195:Disease Models, Animal; D006949:Hyperlipidemias