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VEGF‐A, VEGF‐D, VEGF receptor‐1, VEGF receptor‐2, NF‐KB, and RAGE in atherosclerotic lesions of diabetic Watanabe heritable hyperlipidemic rabbits
Author(s) -
Roy Himadri,
Bhardwaj Shalini,
Babu Mohan,
Kokina Ilze,
Uotila Sanna,
Ahtialansaari Tiia,
Laitinen Teemu,
Hakumaki Juhana,
Laakso Markku,
Herzig KarlHeinz,
YläHerttuala Seppo
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-5029fje
Subject(s) - medicine , endocrinology , angiogenesis , vascular endothelial growth factor , diabetes mellitus , rage (emotion) , neovascularization , receptor , angiopoietin , biology , vegf receptors , neuroscience
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 1 H‐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‐B. VEGF‐A 165 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‐B, RAGE, and inflammatory responses in atherosclerotic lesions in WHHL rabbits.—Roy, H., Bhardwaj, S., Babu, M., Kokina, I., Uotila, S., Ahtialansaari, T., Laitinen, T., Hakumaki, J., Laakso, M., Herzig, K‐H., Ylä‐Herttuala, S. VEGF‐A, VEGF‐D, VEGF receptor‐1, VEGF receptor‐2, NF‐B, and RAGE in atherosclerotic lesions of diabetic Watanabe heritable hyperlipidemic rabbits. FASEB J. 20, E1550 –E1559 (2006)