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Research Summary
Lipid uptake by tissues, atherosclerosis
Research Activities
Regulation of Lipoprotein lipase (LpL): A long-standing interest of this laboratory has been control of LpL, the rate-limiting enzyme required for the conversion of lipoprotein triglyceride into free fatty acids. We have focused on two issues: 1. how LpL, which is expressed in adipocytes and myocytes, transfers to endothelial cells where it interacts with circulating lipoproteins, 2. how mutations of the LpL protein affect its actions in vivo.
Effects of lipid uptake on cardiac function: By creating mice that either overexpress or do not express LpL in the heart, we have obtained new insights into the relationship of fatty acid uptake and genes that affect glucose metabolisms. Although hearts use fatty acids associated with albumin, it appears that much of the energy for heart actions is derived from locally produced fatty acids due to LpL actions on lipoproteins in the cardiac circulation. Moreover, we found that excess cardiac lipid uptake causes dilated cardiomyopathy.
Atherosclerosis: Two issues in atherosclerosis are studied. 1. The role of matrix proteoglycans on development of atherosclerosis in mice. The focus is on the role of perlecan, a basement membrane heparan sulfate proteoglycan. 2. Diabetes is associated with increased atherosclerosis in humans. However, mice only get accelerated atherosclerosis with diabetes if they also develop a more severe hyperlipidemia. By creating models in which additional genes are expressed, we are seeking to find a missing gene in mice that protects them from diabetic atherosclerosis.
Positions & Appointments
| 1996-present |
Attending Physician, Department of Medicine |
Columbia University Medical Center |
New York, NY |
| 1996-present |
Professor of Medicine |
Columbia University, College of Physicians & Surgeons |
New York, NY |
| 1985-present |
Associate Director, Arteriosclerosis Research Center |
Columbia University Medical Center |
New York, NY |
| 1990-1996 |
Associate Attending Physician, Department of Medicine |
Columbia University Medical Center |
New York, NY |
| 1983-1990 |
Assistant Attending Physician, Department of Medicine |
Columbia University Medical Center |
New York, NY |
Education and Training
| 1971-1975 |
Medicine |
Harvard, Boston, MA |
| 1975-1978 |
Int. Medicine |
NYU-Bellevue, NY, NY |
| 1978-1982 |
Endo -Metab/Arteriosclerosis |
Mount Sinai, NY, NY |
Honors and Awards
1981-1986 Clinician-Scientist Award, American Heart Association
1988-1993 Established Fellowship, New York Heart Association
1991 American Society for Clinical Investigation - elected 1991
1992 University Tenure, Columbia University
1999 Association of American Physicians, elected 1999
Session Chairman, American Heart Association Annual Scientific Sessions, 1988,1990,1991,1993,1995,1996,1997,1998
Committees and Society Memberships
Association of American Physicians
American Society for Clinical Investigation
American Heart Association
Fellow, Council on Arteriosclerosis
Nominating and membership committees, 1994-1995
Abstract grading Committee, 1995
Nutrition Committee, 1997
Committee for Scientific Sessions Program, 1997-2000
American Heart Association - New York City Affiliate
Chairman, Committee on Cholesterol Education, 1988-1992
Member - Community Programs, 1988-1990
Professioal Education Committee, 1988-1992
Peer review committee, 1993-1994., Co-chairman 1994-1995, Chairman 1995-1997
Board of Directors (term 1993-1999)
American Heart Association, Heritage Affiliate
Board of Directors, 1998-2000
Chair, Research Council, 1998-2000
New York Diabetes Association
Chairman of the Clinical Society, 1988-1989
Symposium Committee, Chairman, 1987
Clinic Advisory Committee, Chairman, 1985-1987
American Federation for Clinical Research
American College of Physicians
American Association for the Advancement of Science
New York Lipid Club, President, 1992-1993
Selected Publications:
1. Augustus AS, Y Kako, H Yagyu, IJ Goldberg. (2003) Routes of fatty acid delivery to cardiac muscle: Modulation of lipoprotein lipolysis alters uptake of TG-derived fatty acids. Am J Physiol Endocrinol Metab
284:E331-9
2. Yagyu H, G Chen, M Yokoyama, K Hirata, A Augustus, Y Kako, T Seo, Y Hu, EP Lutz, M Merkel, A Bensdadoun, S Homma, IJ Goldberg. (2003) Lipoprotein lipase (LpL) on the surface of cardiomyocytes increased lipid uptake and produced a cardiomyopathy. J Clin Invest
111:419-26
3. Kako Y, M Massé, LS Huang, AR Tall, IJ Goldberg. (2002) Lipoprotein lipase deficiency and CETP in streptozotocin treated apoB-expressing mice. J Lipid R.
43:872-877
4. Yagyu H, EP Lutz, Y Kako, S Marks, Y Hu, SY Choi, A Bensadoun, IJ Goldberg. (2002) VLDL receptor deficient mice have reduced lipoprotein lipase activity. Possible causes of hypertriglyceridemia and reduced body mass with VLDL receptor deficiency. J Biol Chem. :,
277:10037-43
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