CVRI Investigators - Cynthia J. Meininger



		Cynthia J. Meininger, Ph.D. Professor Department of Systems Biology and Translational Medicine Director, CVRI Division of Vascular Biology Education B.A., Cell Biology, 1980, University of South Florida Ph.D., Cell Biology, 1987, Texas A&M University Phone: 254-742-7037 E-mail: cjm@tamu.edu Curriculum vitae pdf \| rtf Laboratory



Meininger, CJ, Cai S, Parker JL, Channon KM, Kelly KA, Becker EJ, Wood MK, Wade LA and Wu G. GTP cyclohydrolase I gene transfer reverses tetrahydrobiopterin deficiency and increases nitric oxide synthesis in endothelial cells and isolated vessels from diabetic rats. FASEB J 18: 1900-1902, 2004 (Full text: doi 10.1096/fj.04-1702fje). Shi W, CJ Meininger, TE Haynes, K Hatakeyama and G Wu. Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial cells, Cell Biochem Biophys 41: 415-434, 2004. Jobgen, WS, SK Fried, WJ Fu, CJ Meininger, G Wu. Regulatory Role for the Arginine-Nitric Oxide Pathway in Metabolism of Energy Substrates. J Nutr Biochem 17: 571-588, 2006. Meininger, CJ, G Wu: “Regulation of Endothelial Cell Proliferation by Nitric Oxide,” In: Redox Cell Biology and Genetics, Methods in Enzymology, (C. Sen/L. Packer, Eds.) NY: Academic Press, 352: 280-295, 2002.		Endothelial Cell Dysfunction in Diabetes My research focuses primarily on the vascular complications of diabetes. Using animal models of human diabetes, we have demonstrated that an inability of endothelial cells to produce nitric oxide may be partly responsible for these vascular complications. We have shown that impaired nitric oxide production in diabetes is due to a deficiency of tetrahydrobiopterin (BH4, an essential co-factor reduced in endothelial cells in diabetes) brought about by decreased expression/activity of an enzyme called GTP cyclohydrolase I (GTPCH), which is the rate-controlling enzyme for the synthesis of BH4. Without BH4, endothelial cells cannot generate nitric oxide. Since BH4 is also one of the most potent endogenous cellular antioxidants, reduced levels of BH4 may also render the endothelial cell more susceptible to oxidative injury. We are developing a gene/drug therapy approach for treating cardiovascular disease associated with diabetes. Targeted nanoparticles will deliver either the gene for GTPCH or BH4 itself into endothelial cells oxidatively damaged by diabetes to correct endothelial GTPCH deficiency, increase tetrahydrobiopterin levels, restore nitric oxide production and reverse the vascular dysfunction seen in diabetes. Our endothelium-targeting nanoparticle approach will not only reverse the damage caused by disease but will increase antioxidant levels to protect the endothelial cells from future damage and/or dysfunction.



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