Member Profile
Edward Fisher
Creating Glucose Responsive Cardiovascular Complications
Grant Number: HL087945
Abstract: The PIs of this application have developed techniques for producing and studying atherosclerosis using funds from the first AMDCC program. Specifically, we have found that streptozotocin-treated mice develop increased atherosclerosis in the presence of a transgene for human aldose reductase (hAR). We have also noted that hearts from these mice have areas of cardiac apoptosis. In addition, we have developed novel methods to study atherosclerosis regression that can be applied to studies of lesions in control and diabetic mice. Aim 1 To create new mouse models of diabetic cardiovascular disease: We propose to create two new genetically altered mice. Aim 1a is to use the tet on system to allow expression of hAR in a time dependent manner. This system will allow us to test whether hAR expression in established lesions alters plaque morphology. These animals can also be used to produce tissue specific expression of hAR. Aim 1b is to produce mice with expression of hAR in cardiomyocytes. These mice, we hypothesize, will develop cardiomyopathy with diabetes. Aim 2 To study the development of vascular lesions in diabetic mice: Mild diabetes due to deficiency of Pdx1 or high fat diets did not alter atherosclerosis in Ldlr-/- mice. In addition, Pdx1 did not affect regression after transplant of arteries containing atherosclerosis. We will use two additional methods to generate hyperglycemia, Akita and high fat diets on the FVB background, in Ldlr-/- mice q hAR. Increased vascular disease in STZ-treated hAR mice could result from greater monocyte/macrophage accumulation in lesions, or could be secondary to a defect in lesion regression. Both processes will be studied in vivo and mechanistic information obtained by studying gene and protein expression.
Institution: |
New York University School of Medicine
550 First Avenue
New York, NY |
Fiscal Year: | 2006 |
Department: | Medicine |
Project Start: | 9/4/2006 |
Project End: | 8/31/2011 |
ICD: | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE |
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Status |
| Effects of High Fat Feeding and Diabetes on Regression of Atherosclerosis Induced by Low-Density Lipoprotein Receptor Gene Therapy in LDL Receptor-Deficient Mice.Willecke F, Yuan C, Oka K, Chan L, Hu Y, Barnhart S, Bornfeldt KE, Goldberg IJ, Fisher EA PLoS ONE, 2015 (10), e0128996 |
| | 26046657 | Published |
| Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.Nagareddy PR, Kraakman M, Masters SL, Stirzaker RA, Gorman DJ, Grant RW, Dragoljevic D, Hong ES, Abdel-Latif A, Smyth SS, Choi SH, Korner J, Bornfeldt KE, Fisher EA, Dixit VD, Tall AR, Goldberg IJ, Murphy AJ Cell Metabolism, 2014 (19), 821 - 835 |
| Submitted Externally | 24807222 | Published |
| Lipolysis, and Not Hepatic Lipogenesis, Is the Primary Modulator of Triglyceride Levels in Streptozotocin-Induced Diabetic Mice.Willecke F, Scerbo D, Nagareddy P, Obunike JC, Barrett TJ, Abdillahi ML, Trent CM, Huggins LA, Fisher EA, Drosatos K, Goldberg IJ Arteriosclerosis, thrombosis, and vascular biology, 2014 (35), 102 - 110 |
| | 25395613 | Published |
| ACAT inhibition reduces the progression of preexisting, advanced atherosclerotic mouse lesions without plaque or systemic toxicity.Rong JX, Blachford C, Feig JE, Bander I, Mayne J, Kusunoki J, Miller C, Davis M, Wilson M, Dehn S, Thorp E, Tabas I, Taubman MB, Rudel LL, Fisher EA Arteriosclerosis, thrombosis, and vascular biology, 2013 (33), 4 - 12 |
| | 23139293 | Published |
| Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis.Nagareddy PR, Murphy AJ, Stirzaker RA, Hu Y, Yu S, Miller RG, Ramkhelawon B, Distel E, Westerterp M, Huang LS, Schmidt AM, Orchard TJ, Fisher EA, Tall AR, Goldberg IJ Cell Metabolism, 2013 (17), 695 - 708 |
| | 23663738 | Published |
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| | 21562077 | Published |
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| | 19333880 | Published |
| Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI.Amirbekian V, Lipinski MJ, Briley-Saebo KC, Amirbekian S, Aguinaldo JG, Weinreb DB, Vucic E, Frias JC, Hyafil F, Mani V, Fisher EA, Fayad ZA Proceedings of the National Academy of Sciences of the United States of America, 2007 (104), 961 - 966 |
| Submitted Externally | 17215360 | Published |
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| Submitted Externally | 17451174 | Published |
| Recipes for Creating Animal Models of Diabetic Cardiovascular DiseaseWilla 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 |
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| | 16537455 | Published |
| Serial studies of mouse atherosclerosis by in vivo magnetic resonance imaging detect lesion regression after correction of dyslipidemia.Trogan E, Fayad ZA, Itskovich VV, Aguinaldo JG, Mani V, Fallon JT, Chereshnev I, Fisher EA Arteriosclerosis, thrombosis, and vascular biology, 2004 (24), 1714 - 1719 |
| | 15256400 | Published |
| Improved insulin sensitivity is associated with restricted intake of dietary glycoxidation products in the db/db mouse.Hofmann SM, Dong HJ, Li Z, Cai W, Altomonte J, Thung SN, Zeng F, Fisher EA, Vlassara H Diabetes, 2002 (51), 2082 - 2089 |
| Submitted Externally | 12086936 | Published |
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