Nobuyo N. Maeda, PhD
Robert H. Wagner Distinguished Professor
We are interested in the genetics and molecular pathology of atherosclerosis, a complex multi-factorial vascular disease and the major cause of death and disabilities in the North America. Our approach consists of a series of experiments with mice carrying modifications in various genes specifying components important in lipid transport and clearance, and in genes important for the maintenance of vascular function and antioxidant defense. Using the spontaneous atherosclerosis in mice lacking apolipoprotein E as a basis, we have been studying interactions between genetic and environmental factors, and the effects on atherogenesis of other common disease conditions such as insulin resistance, diabetes and hypertension.
Maeda N, Johnson L, Kim S, Hagaman J, Friedman M, Reddick R. Anatomical differences and atherosclerosis in apolipoprotein E-deficient mice with 129/SvEv and C57BL/6 genetic backgrounds. Atherosclerosis. 2007 Jan 30.
Altenburg MK, Johnson LA, Wilder JC, Maeda N. Apolipoprotein E4 in macrophages enhances atherogenesis in an LDL receptor dependent manner. J Biol Chem. 282:7817-7824 (2007).
Jones C, Garuti R, Michaely P, Li WP, Maeda N, Cohen JC, Herz J, Hobbs HH. Disruption of LDL but not VLDL clearance in autosomal recessive hypercholesterolemia. J Clin Invest. 117:165-74. (2007).
Muallem H, North KE, Kakoki M, Wojczynski MK, Li X, Grove M, Boerwinkle E, Wilhelmsen KC, Heiss G, Maeda N. Quantitative effects of common genetic variations in the 3'UTR of the human LDL-receptor gene and their associations with plasma lipid levels in the Atherosclerosis Risk in Communities study. Hum Genet. 121:421-431 (2007).
Yi X and Maeda N. Alpha-Lipoic Acid Prevents the Increases in Atherosclerosis Induced by Diabetes in Apolipoprotein E-Deficient Mice Fed High Fat/Low Cholesterol Diet. Diabetes 55(8):2238-44 (2006).
Tsai Y-S, Pandse A, Moy SS, Mohri I, Perez A, Crawley JN, Suzuki K and Maeda N. A de novo deafwaddler mutation of Pmca2 arising in ES cells and hitchhiking with a targeted modification of the Pparg gene. Mammalian Genome, 17:716-22 (2006).
Nishikimi T, Hagaman JR, Takahashi N, Kim HS, Matsuoka H, Smithies O, Maeda N. Increased susceptibility to heart failure in response to volume overload in mice lacking natriuretic peptide receptor-A gene. Cardiovasc Res. 66:94-103. (2005).
Yi X, Maeda N. Endogenous production of lipoic acid is essential for mouse development. Mol Cell Biol. 25:8387-92 (2005).
Tsai YS, Kim HJ, Takahashi N, Kim HS, Hagaman JR, Kim JK, Maeda N. Hypertension and abnormal fat distribution but not insulin resistance in mice with P465L-PPARγ. J Clin Invest. 14:240-249. (2004).
Malloy SI, Altenburg MK, Knouff, C, Lanningham-Foster L, Parks JS, Maeda N. Harmful Effects of Increased LDLR Expression in Mice with Human APOE*4 but not APOE*3. Arterioscler Thromb Vasc Biol. 24:91-97. (2004).
Knowles, JW, Erickson, L, Guy, V, Sigel, C, Wilder, JC, and Maeda, N. Common Variations in Noncoding Regions of the Human Natriuretic Peptide Receptor A Gene Have Quantitative Effects. J. Hum. Genet. 112:62-70 (2003).
Nakata, Y., and Maeda, N. Vulnerable Atherosclerotic Plaque Morphology in Apolipoprotein E-Deficient Mice Unable to Make Ascorbic Acid. Circulation 105:1485-1490 (2002).
Hodgin, JB, Knowles, JW, Kim, H-S, Smithies, O, and Maeda, N. Interactions between endothelial nitric oxide synthase and sex hormones in vascular protection in mice. J. Clin. Invest. 109:541-548 (2002).
Hodgin, J.B., Krege, J.H., Reddick, R.L., Korach, K.S., Smithies, O., and Maeda, N. Estrogen receptor alpha is a major mediator of the atheroprotective effect of 17β-estradiol in Apoe-/- mice, J. Clin. Invest. 107:333-340 (2001).
Dawson, T.C., Beck, M.A., Kuziel, W.A., Henderson, F., and Maeda, N. Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus Am. J. Pathol. 156:1951-1959. (2000).
Knowles, J.W., Reddick, R.L., Jennette, J.C., Shesely, E.G., Smithies, O., and Maeda, N. Enhanced atherosclerosis and kidney dysfunction in eNOS-/-•apoE-/- mice are ameliorated by enalapril treatment J. Clin. Invest. 105:451-458 (2000).
Sullivan, P.M., Mezdour, H., Quarfordt, S.H. and Maeda, N. Type III Hyperlipoproteinemia and Spontaneous Atherosclerosis in Mice Resulting from Gene Replacement of Mouse Apoe with Human APOE*2, J. Clin. Invest. 102(1):130-135 (1998).
Oliver, P.M., Fox, J.E., Kim, R., Rockman, H.A., Kim, H.-S., Reddick, R.L., Pandey, K.N., Milgram, S.L., Smithies, O., and Maeda, N. Hypertension, Cardiac Hypertrophy, and Sudden Death in Mice Lacking Natriuretic Peptide Receptor A, Proc. Natl. Acad. Sci. USA 94:14730-14735 (1997).
Reddick, R.L., Zhang, S.H. and Maeda, N. Atherosclerosis in mice lacking apolipoprotein E: Evaluation of lesional development and progression. Arteriosclerosis and Thrombosis 14:141-147 (1994).
Zhang, S.H., Reddick, R.L., Piedrahita, J.A. and Maeda, N. Spontaneous Hypercholestrolemia and Arterial Lesions in Mice Lacking Apolipoprotein E. Science 258:468-471 (1992).