Research Interests
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.
Selected Publications
Kayashima Y, Tomita H, Zhilicheva S, Kim S, Kim HS, Bennett BJ, Maeda N. Quantitative Trait Loci Affecting Atherosclerosis at the Aortic Root Identified in an Intercross between DBA2J and 129S6 Apolipoprotein E-Null Mice. PLoS One. 2014 Feb 20;9(2):e88274. PMCID: PMC3930552
Perez-Diaz S. Johnson LA, Dekoon RM, Moreno-Navarrete, Alxate O, Fernandez-Real, Maeda N, Arbones-Mainer JM. Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability. FASEB J. 2014 May 8 PMID: 24812087
Hiller S, Dekroon R, Xu L, Robinette J, Winnik W, Alzate O, Simington S, Maeda N, Yi X. a-Lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice. Free Radic Biol Med. 2014 Mar 24;71C:362-367. PMID: 24675228, PMCID: PMC3988092
Johnson LA, Olsen RH, Merkens LS, DeBarber A, Steiner RD, Sullivan PM, Maeda N, Raber J. Apolipoprotein E-low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner. Neurobiol Dis. 2014 Apr;64:150-62. PMID: 24412220, PMCID: PMC3936477
Johnson LA, Kim HS, Knudson MJ, Nipp CT, Yi X, Maeda N. Diabetic atherosclerosis in APOE*4 mice: Synergy between lipoprotein metabolism and vascular inflammation. J Lipid Res. 2013 Feb;54(2):386-96. PMCID: PMC3389794
Fox RG, Magness ST, Kujoth GC, Prolla TA, Maeda N. Mitochondrial DNA polymerase editing mutation, PolgD257A, disturbs stem-progenitor cell cycling in the small intestine and restricts excess fat absorption. Am J Physiol Gastrointest Liver Physiol. 2012, May;302(9):G914-24. PMCID: PMC3362078
Maeda N. Development of apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):1957-62. PMCID: PMC3286619
Johnson LA, Arbones-Mainar JM, Fox RG, Pendse AA, Altenburg MK, Kim HS, Maeda N. Apolipoprotein E4 exaggerates diabetic dyslipidemia and atherosclerosis in mice lacking the LDL receptor. Diabetes. 2011 Sep;60(9):2285-94. PMCID: PMC3161311
Fox R, Kim HS, Reddick RL, Kujoth GC, Prolla TA, Tsutsumi S, Wada Y, Smithies O, Maeda N. Mitochondrial DNA polymerase editing mutation, PolgD257A, reduces the diabetic phenotype of Akita male mice by suppressing appetite. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8779-84. PMCID: PMC3102415
Doherty HE, Kim HS, Hiller S, Sulik KK, Maeda N. A mouse strain where basal connective tissue growth factor gene expression can be switched from low to high. PLoS One. 2010 Sep 22;5(9):e12909. PMCID: PMC2943916
Pendse AA, Johnson LA, Tsai YS, Maeda N. Pparg-P465L mutation worsens hyperglycemia in Ins2-Akita female mice via adipose-specific insulin resistance and storage dysfunction. Diabetes. 2010 Nov;59(11):2890-7. PMCID: PMC2963548
Arbones JM, Johnson LA, Altenburg MK, Kim HS, Maeda N. Impaired adipogenic response to thiazolidinediones in mice expressing human apolipoprotein E4. FASEB J. 2010 Oct;24(10):3809-18. PMCID: PMC2996914
Tomita H, Zhilicheva S, Kim S, Maeda N. Aortic Arch Curvature and Atherosclerosis Have Overlapping Quantitative Trait Loci in Crosses Between 129S6/SvEvTac and C57BL/6J Apolipoprotein E-Null Mice. Circ Res. 2010 Apr2;106(6) :1052-60. PMC2848914
Tsai YS, Xu L, Smithies O, Maeda N. Genetic variations in peroxisome proliferator-activated receptor gamma expression affect blood pressure. Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19084-9. PMCID: PMC2771745
Franceschini N, Muallem H, Rose KM, Boerwinkle E, Maeda N. Low density lipoprotein receptor polymorphisms and the risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. J Thromb Haemost. 2009 Mar;7(3):496-8. PMCID: PMC2656439
Arbones-Mainar JM, Johnson LA, Altenburg MK, Maeda N. Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein E3 and E4 in mice. Int. J. of Obesity. 2008 Oct;32(10):1595-605. PMCID: PMC2805194.
Altenburg M, Arbones-Mainar J, Johnson L, Wilder J, Maeda N. Human LDL receptor enhances sequestration of ApoE4 and VLDL remnants on the surface of hepatocytes but not their internalization in mice. Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1104-10. PMID:18369154
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 ;195(1):75-82. PMID: 17275002
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). PMID: 17273844
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).
