title: VEGF-A, VEGF-D, VEGF receptor-1, VEGF receptor-2, NF-kappaB, and RAGE in atherosclerotic lesions of diabetic Watanabe heritable hyperlipidemic rabbits.
abstract: Plaque angiogenesis may be associated with the development of unstable and vulnerable plaques. Vascular endothelial growth factors (VEGFs) are potent angiogenic factors that can affect plaque neovascularization. Our objective was to determine the effect of diabetes on atherosclerosis and on the expression of angiogenesis-related genes in atherosclerotic lesions. Alloxan was used to induce diabetes in male Watanabe heritable hyperlipidemic (WHHL) rabbits that were sacrificed 2 and 6 months after the induction of diabetes. Nondiabetic WHHL rabbits served as controls. Blood glucose (Glc), serum-free fatty acids (FFA), and serum triglyceride levels were significantly higher in diabetic rabbits. Accelerated atherogenesis was observed in the diabetic WHHL rabbits together with increased intramyocellular lipids (IMCL), as determined by 1H-NMR spectroscopy. Atherosclerotic lesions in the diabetic rabbits had an increased content of macrophages and showed significant increases in immunostainings for vascular endothelial growth factor (VEGF)-A, VEGF-D, VEGF receptor-1, VEGF receptor-2, RAGE, and NF-kappaB. VEGF-A165 and VEGFR-2 mRNA levels were significantly increased in aortas of the diabetic rabbits, where a trend toward increased plaque vascularization was also observed. These results suggest that diabetes accelerates atherogenesis, up-regulates VEGF-A, VEGF-D, and VEGF receptor-2 expression, and increases NF-kappaB, RAGE, and inflammatory responses in atherosclerotic lesions in WHHL rabbits.
authors.affiliation: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland.
authors.forename: Himadri
authors.initials: H
authors.lastname: Roy
authors.forename: Shalini
authors.initials: S
authors.lastname: Bhardwaj
authors.forename: Mohan
authors.initials: M
authors.lastname: Babu
authors.forename: Ilze
authors.initials: I
authors.lastname: Kokina
authors.forename: Sanna
authors.initials: S
authors.lastname: Uotila
authors.forename: Tiia
authors.initials: T
authors.lastname: Ahtialansaari
authors.forename: Teemu
authors.initials: T
authors.lastname: Laitinen
authors.forename: Juhana
authors.initials: J
authors.lastname: Hakumaki
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herzig
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000496:Alloxan; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D006949:Hyperlipidemias / Q000150:complications; D008297:Male; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D000067759:Receptor for Advanced Glycation End Products; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics*; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics*; D042643:Vascular Endothelial Growth Factor D / Q000032:analysis / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000235:genetics
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; D000496:Alloxan; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2