Atherosclerosis and the protective role played by different proteins in apolipoprotein E-deficient mice.
The aim of the present study was to analyze the early events in atherogenesis and the role of pro- or anti-atherosclerotic proteins in the development of atherosclerotic lesions. We used apolipoprotein E-deficient (E(0)) mice that spontaneously develop hypercholesterolemia and atherosclerotic lesions in the aorta in a time-dependent manner. Aortas of mice aged 6, 8, 10 and 12 weeks were examined to determine histopathological changes. In mice aged 8-12 weeks, developing atherosclerotic lesions were present in different regions of the aortas. These lesions protruded into the lumen of the vessel and showed lipid deposits, lipid-filled macrophages and extensive accumulation of collagen and elastic fibers throughout the entire arterial wall. A parallel immunohistochemical study included analysis of three proteins known to be involved in atherosclerosis, i.e. inducible nitric oxide synthase (iNOS, NOS2), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP2). Increased immunolabelling of iNOS and VEGF accompanied atherosclerosis development in E(0) mice aged 8, 10 and 12 weeks. On the contrary, immunolabelling for MMP2 was negative in E(0) mice aged 10 and 12 weeks. Our results indicate morphological alterations in the Tunica intima and Tunica media of atherosclerotic aortas and possible protective roles for iNOS and VEGF proteins against atherosclerosis development. These data may be relevant for developing therapeutic strategies for atherosclerosis development.
Fabrizio Rodella
Luigi
L
Division of Human Anatomy, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Viale Europa, 11, Brescia 25123, Italy.
Bonomini
Francesca
F
Rezzani
Rita
R
Tengattini
Sandra
S
Hayek
Tony
T
Aviram
Michael
M
Keidar
Shlomo
S
Coleman
Raymond
R
Bianchi
Rossella
R
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D001057:Apolipoproteins E; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D020778:Matrix Metalloproteinase 2