Nobuyo Maeda

Personal Information
Title Professor
Expertise Cardiovascular
Institution University of North Carolina
Data Summary
TypeCount
Grants/SubContracts 1
Progress Reports 5
Presentations 4
Publications 29
Protocols 1
Committees 1
Experiments 0
Strains 12
Models 0

Dyslipidemia, Lipoic Acid and Diabetic Vascular Complications in Humanized
Grant Number: HL087946

Abstract: While diabetes mellitus can lead to serious damage to many organs, cardiovascular diseases are the major cause of death and morbidity in diabetic patients. Overall, patients with diabetes have a three to five fold increased risk of coronary artery diseases compared to non-diabetics. Our goal is to use mouse genetics for identifying genetic risk factors for the vascular complications of diabetes and for unraveling underlying mechanisms. Although a significant increase in atherosclerosis by diabetes has been demonstrated in atherogenic mouse models, none of these mouse models faithfully replicates the types of dyslipidemia associated with diabetes in humans. We postulate that this failure is due to differences in the relative levels of plasma low density lipoprotein (LDL) and plasma high density lipoprotein (HDL) that are controlled by genetic differences between the two species and genetic polymorphisms in humans. Thus our first hypothesis is that humanizing genes that are involved in lipoprotein metabolism in mice so that they develop a more human-like diabetic dyslipidemia will cause them to replicate better the cardiovascular problems of human diabetic patients. We will test this hypothesis in Specific Aim 1 by inducing diabetes in mice with humanized apoE of the three isoforms (E2, E3, and E4) and humanized LDL receptor (LDLR), with or without overexpression of human apoB. We predict that this will lead to diabetic dyslipidemia and accelerated atherosclerosis in an apoE isoform dependent manner. Our second hypothesis is that since diabetes is generally acknowledged to induce oxidative stress, genetically determined differences in the levels of endogenous anti-oxidants affect the development of cardiovascular complications,. To test this hypothesis, we propose in Specific Aim 2 to develop a new mouse model with a genetically controlled reduction in the production of the endogenous antioxidant lipoic acid (LA). We will modify the LA synthase (Lias) gene in such a way that the stability of Lias mRNA will be drastically reduced in a tissue specific fashion. Our hypothesis predicts that reduced production of LA will increase the oxidative stress already present in diabetic mice and enhance their development of vascular complications. In Specific Aim 3, we propose to combine human-like diabetic dyslipidemia with genetically reduced antioxidant capacity due to LA deficiency to test our overall thesis that interactions between genetic polymorphic differences affecting lipid profiles and genetic differences affecting endogenous antioxidant levels determine the degree to which diabetes enhances cardiovascular disease.


Institution: University of North Carolina
9201 University City Blvd
Charlotte, NC
Fiscal Year:2006
Department:PATHOLOGY AND LAB MEDICINE
Project Start: 9/4/2006
Project End: 8/31/2011
ICD: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Progress Reports

No funding program application progress reports found.

Annual Reports

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Maeda, Nobuyo (2007)
2007Annual Report
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Maeda, Nobuyo (20080
2008Annual Report
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Maeda, Nobuyo (2009)
2009Annual Report
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Maeda, Nobuyo (2010)
2010Annual Report
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Maeda, Nobuyo (2011)
2011Annual Report
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 PublicationAltmetricsSubmitted ByPubMed IDStatus

Year: 2016; Items: 1

 
Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy.
Xu L, Hiller S, Simington S, Nickeleit V, Maeda N, James LR, Yi X
PLoS ONE, 2016 (11)
27706190
Published

Year: 2014; Items: 2

 
a-Lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice.
Hiller S, DeKroon R, Xu L, Robinette J, Winnik W, Alzate O, Simington S, Maeda N, Yi X
Free radical biology & medicine, 2014 (71), 362 - 367
24675228
Published
 
Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.
Perez-Diaz S, Johnson LA, DeKroon RM, Moreno-Navarrete JM, Alzate O, Fernandez-Real JM, Maeda N, Arbones-Mainar JM
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014 (28), 3769 - 3779
Submitted Externally
24812087
Published

Year: 2013; Items: 2

 
Diabetic atherosclerosis in APOE*4 mice: synergy between lipoprotein metabolism and vascular inflammation.
Johnson LA, Kim HS, Knudson MJ, Nipp CT, Yi X, Maeda N
Journal of lipid research, 2013 (54), 386 - 396
23204275
Published
 
Connective tissue growth factor (CTGF) expression modulates response to high glucose.
James LR, Le C, Doherty H, Kim HS, Maeda N
PLoS ONE, 2013 (8), e70441
23950936
Published

Year: 2012; Items: 5

 
Reduced expression of lipoic acid synthase accelerates diabetic nephropathy.
Yi X, Xu L, Hiller S, Kim HS, Nickeleit V, James LR, Maeda N
Journal of the American Society of Nephrology : JASN, 2012 (23), 103 - 111
22021711
Published
 
eNOS deficiency acts through endothelin to aggravate sFlt-1-induced pre-eclampsia-like phenotype.
Li F, Hagaman JR, Kim HS, Maeda N, Jennette JC, Faber JE, Karumanchi SA, Smithies O, Takahashi N
Journal of the American Society of Nephrology : JASN, 2012 (23), 652 - 660
22282588
Published
 
Mitochondrial DNA polymerase editing mutation, PolgD257A, disturbs stem-progenitor cell cycling in the small intestine and restricts excess fat absorption.
Fox RG, Magness S, Kujoth GC, Prolla TA, Maeda N
American journal of physiology. Gastrointestinal and liver physiology, 2012 (302), G914 - G924
22345551
Published
 
Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-? in apolipoprotein E-Null mice.
Pendse AA, Johnson LA, Kim HS, McNair M, Nipp CT, Wilhelm C, Maeda N
Arteriosclerosis, thrombosis, and vascular biology, 2012 (32), 1436 - 1444
22539598
Published
 
22658261
Published

Year: 2011; Items: 6

 
a-Lipoic acid protects diabetic apolipoprotein E-deficient mice from nephropathy.
Yi X, Nickeleit V, James LR, Maeda N
Journal of diabetes and its complications, 2011 (25), 193 - 201
20801062
Published
 
A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy.
Wang CH, Li F, Hiller S, Kim HS, Maeda N, Smithies O, Takahashi N
Proceedings of the National Academy of Sciences of the United States of America, 2011 (108), 2070 - 2075
21245338
Published
 
A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy.
Wang CH, Li F, Hiller S, Kim HS, Maeda N, Smithies O, Takahashi N
Proceedings of the National Academy of Sciences of the United States of America, 2011 (108), 2070 - 5
21245338
Published
 
Mitochondrial DNA polymerase editing mutation, PolgD257A, reduces the diabetic phenotype of Akita male mice by suppressing appetite.
Fox R, Kim HS, Reddick RL, Kujoth GC, Prolla TA, Tsutsumi S, Wada Y, Smithies O, Maeda N
Proceedings of the National Academy of Sciences of the United States of America, 2011 (108), 8779 - 8784
21555558
Published
 
Submitted Externally
21743035
Published
 
Apolipoprotein E4 exaggerates diabetic dyslipidemia and atherosclerosis in mice lacking the LDL receptor.
Johnson LA, Arbones-Mainar JM, Fox RG, Pendse AA, Altenburg MK, Kim HS, Maeda N
Diabetes, 2011 (60), 2285 - 2294
21810592
Published

Year: 2010; Items: 4

 
20347443
Published
 
Impaired adipogenic response to thiazolidinediones in mice expressing human apolipoproteinE4.
Arbones-Mainar JM, Johnson LA, Altenburg MK, Kim HS, Maeda N
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010 (24), 3809 - 3818
20501792
Published
 
Elevated tissue factor expression contributes to exacerbated diabetic nephropathy in mice lacking eNOS fed a high fat diet
F . L I , C.-H. WANG, J .-G. WANG, T. THAI , G. BOYSEN, L . XU, A. L . TURNER, A. S . WOLBERG, N. MACKMAN, N. MAEDA and N. TAKAHASHI
Journal of thrombosis and haemostasis : JTH, 2010 (8), 2122 - 2132
20626618
Published
 
20724579
Published

Year: 2009; Items: 1

 
Mice with heterozygous deficiency of lipoic acid synthase have an increased sensitivity to lipopolysaccharide-induced tissue injury.
Yi X, Kim K, Yuan W, Xu L, Kim HS, Homeister JW, Key NS, Maeda N
Journal of leukocyte biology, 2009 (85(1)), 146 - 153
18845616
Published

Year: 2008; Items: 1

 
Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein E3 and E4 in mice.
Arbones-Mainar JM, Johnson LA, Altenburg MK, Maeda N
International journal of obesity (2005), 2008 (32(10)), 1595 - 1605
18725890
Published

Year: 2007; Items: 1

 
Recipes for Creating Animal Models of Diabetic Cardiovascular Disease
Willa Hsueh, E. Dale Abel, Jan L. Breslow, Nobuyo Maeda, Richard C. Davis, Edward A. Fisher, Hayes Dansky, Donald A. McClain, Richard McIndoe, Momtaz K. Wassef, Cristina Rabadan-Diehl, Ira J. Goldberg
Circulation research, 2007 (100), 1415 - 1427
17525381
Published

Year: 2006; Items: 3

 
Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors
Kakoki M, Kizer CM, Yi X, Takahashi N, Kim H-S, Bagnell CR, Edgell CJS, Maeda N, Jennette JC, Smithies O
The Journal of clinical investigation, 2006 (116), 1302 - 1309
16604193
Published
 
A de novo deafwaddler mutation of Pmca2 arising in ES cells and hitchhiking with a targeted modification of the Pparg gene.
Tsai YS, Pendse A, Moy SS, Mohri I, Perez A, Crawley JN, Suzuki K, Maeda N
Mammalian genome : official journal of the International Mammalian Genome Society, 2006 (17(7)), 716 - 722
16845470
Published
 
16873686
Published

Year: 2005; Items: 2

 
PPARgamma: a critical determinant of body fat distribution in humans and mice.
Tsai YS, Maeda N
Trends in cardiovascular medicine, 2005 (15(3)), 81 - 85
16039966
Published
 
Endogenous production of lipoic acid is essential for mouse development.
Yi X, Maeda N
Molecular and cellular biology, 2005 (25(18)), 8387 - 8392
16135825
Published

Year: 2004; Items: 1

 
Hypertension and abnormal fat distribution but not insulin resistance in mice with P465L PPARgamma.
Tsai YS, Kim HJ, Takahashi N, Kim HS, Hagaman JR, Kim JK, Maeda N
The Journal of clinical investigation, 2004 (114), 240 - 249
15254591
Published

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Maeda, Nobuyo (2006)
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Maeda, Nobuyo (2007)
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Maeda, Nobuyo (2009)
2009Presentation
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No experiments found.

No models found.