Ira Goldberg

Personal Information
Title Professor
Expertise Cardiovascular
Institution New York University School of Medicine
Data Summary
TypeCount
Grants/SubContracts 3
Progress Reports 9
Presentations 3
Publications 26
Protocols 0
Committees 2
Experiments 0
Strains 1
Models 0

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

SubContract(s)


Glucose Regulation of Hypertriglyceridemia
Patients with metabolic syndrome (MetS), type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) are at increased risk of cardiovascular disease (CVD), but the underlying mechanisms remain poorly understood. Many lines of evidence indicate that elevated levels of plasma triglyceride (TG) are causal, especially in T2DM. Moreover, hypertriglyceridemia (hyperTG) is a likely cause of changes in circulating levels of HDL cholesterol (HDL-C), a negative risk factor for CVD. We propose to determine the pathophysiology responsible for hyperTG in humans with diabetes and how hyperglycemia affects levels of plasma TG and other lipoproteins. Moreover, we will assess whether hyperTG and diabetes alter HDL function. This Pilot and Feasibility application has two specific aims. Aim 1 is to determine why glucose reduction reduces TG levels in diabetic mice. We will determine whether this is due to a reduction in TG production or greater TG clearance. Aim 2 will determine the effects of acute hyperTG and insulin-deficient diabetes on HDL composition and function. We will determine the structural and lipid changes that occur in HDL from LpL-deleted mice and whether these HDL are defective in promoting cholesterol efflux from macrophages. The studies will lay the foundation for future investigations of how altering circulating lipids in the setting of diabetes impact atherosclerosis.

Hyperglycemia and white blood cell biology
Several complications of diabetes may be exacerbated by inflammation. Whether this is due to hyperglycemia, defective insulin actions, or other metabolic alterations of diabetes is unknown. In addition, both local tissue inflammation and changes in the biology of circulating white blood cells (WBCs) could lead to pathological changes in organs and vascular tissues. In this regard, we have recently found that loss of WBCs from atherosclerotic mouse lesions is defective in the presence of streptozotocin diabetes. Moreover, we provide Preliminary Results showing that changes in circulating WBCs that occur with diabetes are corrected by glucose reduction using inhibitors to the sodium glucose co-transporter 2 (SGLT2). Thus, the studies proposed will allow us to “understand the possible in vivo efficacy of a promising new therapy for diabetes”, glucose reduction via inhibition of SGLT2. This Pilot application has two aims: Aim 1. To determine if hyperglycemia reduction leads to an alteration in the inflammatory state of circulating monocytes and neutrophils. Aim 2. To determine whether glucose reduction in STZ-treated LDL receptor knockout mice with atherosclerosis will reduce the inflammatory profile of lesional CD68+ cells. Techniques to lower glucose in diabetic mice, isolate circulating monocytes subsets (Lys6-C hi and lo) and granulocytes by FACS, and vascular wall CD68+ cells by laser capture microdissection are in hand. We expect that our studies will clarify the importance of hyperglycemia alone in altering the inflammatory status of circulating and vascular WBCs.




 PublicationAltmetricsSubmitted ByPubMed IDStatus

Year: 2015; Items: 2

 
The evolving understanding of the contribution of lipid metabolism to diabetic kidney disease.
Stadler K, Goldberg IJ, Susztak K
Current diabetes reports, 2015 (15), 611
25957525
Published
 
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

Year: 2014; Items: 4

 
Aldose reductase drives hyperacetylation of Egr-1 in hyperglycemia and consequent upregulation of proinflammatory and prothrombotic signals.
Vedantham S, Thiagarajan D, Ananthakrishnan R, Wang L, Rosario R, Zou YS, Goldberg I, Yan SF, Schmidt AM, Ramasamy R
Diabetes, 2014 (63), 761 - 774
Submitted Externally
24186862
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
 
Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development.
Kang HM, Ahn SH, Choi P, Ko YA, Han SH, Chinga F, Park AS, Tao J, Sharma K, Pullman J, Bottinger EP, Goldberg IJ, Susztak K
Nature medicine, 2014 (21), 37 - 46
25419705
Published

Year: 2013; Items: 2

 
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
 
Lipids and the endothelium: bidirectional interactions.
Goldberg IJ, Bornfeldt KE
Current atherosclerosis reports, 2013 (15), 365
Submitted Externally
24037142
Published

Year: 2012; Items: 3

 
Lipid metabolism and toxicity in the heart.
Goldberg IJ, Trent CM, Schulze PC
Cell Metabolism, 2012 (15), 805 - 812
22682221
Published
 
Sphingolipids, lipotoxic cardiomyopathy, and cardiac failure.
Park TS, Goldberg IJ
Heart failure clinics, 2012 (8), 633 - 641
22999245
Published
 
Cardiomyocyte aldose reductase causes heart failure and impairs recovery from ischemia.
Son NH, Ananthakrishnan R, Yu S, Khan RS, Jiang H, Ji R, Akashi H, Li Q, O'Shea K, Homma S, Goldberg IJ, Ramasamy R
PLoS ONE, 2012 (7), e46549
Submitted Externally
23029549
Published

Year: 2011; Items: 3

 
Diabetes adversely affects macrophages during atherosclerotic plaque regression in mice.
Parathath S, Grauer L, Huang LS, Sanson M, Distel E, Goldberg IJ, Fisher EA
Diabetes, 2011 (60), 1759 - 1769
21562077
Published
 
Human aldose reductase expression accelerates atherosclerosis in diabetic apolipoprotein E-/- mice.
Vedantham S, Noh H, Ananthakrishnan R, Son N, Hallam K, Hu Y, Yu S, Shen X, Rosario R, Lu Y, Ravindranath T, Drosatos K, Huggins LA, Schmidt AM, Goldberg IJ, Ramasamy R
Arteriosclerosis, thrombosis, and vascular biology, 2011 (31), 1805 - 1813
Submitted Externally
21636809
Published
 
Mice with cardiac overexpression of peroxisome proliferator-activated receptor ? have impaired repolarization and spontaneous fatal ventricular arrhythmias.
Morrow JP, Katchman A, Son NH, Trent CM, Khan R, Shiomi T, Huang H, Amin V, Lader JM, Vasquez C, Morley GE, D'Armiento J, Homma S, Goldberg IJ, Marx SO
Circulation, 2011 (124), 2812 - 2821
22124376
Published

Year: 2010; Items: 3

 
Creating and curing fatty hearts.
Khan RS, Drosatos K, Goldberg IJ
Current opinion in clinical nutrition and metabolic care, 2010 (13), 145 - 149
20010095
Published
 
20466987
Published
 
PPARg-induced cardiolipotoxicity in mice is ameliorated by PPARa deficiency despite increases in fatty acid oxidation.
Son NH, Yu S, Tuinei J, Arai K, Hamai H, Homma S, Shulman GI, Abel ED, Goldberg IJ
The Journal of clinical investigation, 2010 (120), 3443 - 3454
20852389
Published

Year: 2009; Items: 2

 
Skeletal muscle-specific deletion of lipoprotein lipase enhances insulin signaling in skeletal muscle but causes insulin resistance in liver and other tissues.
Wang H, Knaub LA, Jensen DR, Young Jung D, Hong EG, Ko HJ, Coates AM, Goldberg IJ, de la Houssaye BA, Janssen RC, McCurdy CE, Rahman SM, Soo Choi C, Shulman GI, Kim JK, Friedman JE, Eckel RH
Diabetes, 2009 (58(1)), 116 - 124
18952837
Published
 
Regulation of plasma fructose and mortality in mice by the aldose reductase inhibitor lidorestat.
Noh HL, Hu Y, Park TS, DiCioccio T, Nichols AJ, Okajima K, Homma S, Goldberg IJ
The Journal of pharmacology and experimental therapeutics, 2009 (328(2)), 496 - 503
18974362
Published

Year: 2008; Items: 2

 
Decreased lipoprotein clearance is responsible for increased cholesterol in LDL receptor knockout mice with streptozotocin-induced diabetes.
Goldberg IJ, Hu Y, Noh HL, Wei J, Huggins LA, Rackmill MG, Hamai H, Reid BN, Blaner WS, Huang LS
Diabetes, 2008 (57(6)), 1674 - 1682
18346984
Published
 
Ceramide is a cardiotoxin in lipotoxic cardiomyopathy.
Park TS, Hu Y, Noh HL, Drosatos K, Okajima K, Buchanan J, Tuinei J, Homma S, Jiang XC, Abel ED, Goldberg IJ
Journal of lipid research, 2008 (49), 2101 - 2112
18515784
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: 2

 
Diabetic Vascular Disease. An Experimental Objective
Ira J. Goldberg and Hayes M. Dansky
Arteriosclerosis, thrombosis, and vascular biology, 2006 (26), 1693 - 1701
16763160
Published
 
Addition of dietary fat to cholesterol in the diets of LDL receptor knockout mice: effects on plasma insulin, lipoproteins, and atherosclerosis.
Wu L, Vikramadithyan R, Yu S, Pau C, Hu Y, Goldberg IJ, Dansky HM
Journal of lipid research, 2006 (47), 2215 - 2222
Submitted Externally
16840797
Published

Year: 2005; Items: 1

 
Human Aldose Reductase Expression Accelerates Diabetic Atherosclerosis in Transgenic Mice
Reeba K. Vikramadithyan, Yunying Hu, Hye-Lim Noh, Chien-Ping Liang, Kellie Hallam, Alan R. Tall, Ravichandran Ramasamy and Ira J. Goldberg
The Journal of clinical investigation, 2005 (115), 2434 - 2443
16127462
Published

Year: 2004; Items: 1

 
Effects of streptozotocin-induced diabetes in apolipoprotein AI deficient mice
Ira J. Goldberg, Aaron Isaacs, Ephraim Sehayek, Jan L. Breslow, Li-Shin Huang
Atherosclerosis, 2004 (172), 47 - 53
14709356
Published

Drag a column header and drop it here to group by that column
Title YearTypeOptions
Goldberg, Ira (2005)
2005Presentation
View
Goldberg, Ira (2007)
2007Presentation
View
Goldberg, Ira (2009)
2009Presentation
View

No protocols found.

No experiments found.

No models found.