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Vice Chair
and
Professor,
Medicine
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Professor,
Physiology
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Director,
Electrocardiographic Laboratory,
Graduate Medical Education
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Co-Director,
UCLA Specialty Training and Advanced Research (STAR) Program
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Member,
ACCESS Program: Dept. of Molecular, Cell & Integrative Physiology,
California NanoSystems Institute
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Education: |
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Degrees:
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Ph.D., The Johns Hopkins University School of Medicine, 1983
B.S., University of Arizona, 1977
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M.D.:
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1983 Johns Hopkins University School of Medicine
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Certifications: |
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Certifications:
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1989 American Board of Internal Medicine
1986 American Board of Internal Medicine
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Honors and Awards: |
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AHA Jeffrey M. Hoeg Award, Basic Science and Clinical Research
Franklin D. Murphy, M.D., Prize for Research
Royal College of Physicians of Edinburgh, Davidson Memorial Endowed Lectureship
Stein/Oppenheimer Award for Biomedical Research
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Contact Information:
| Mailing Address: |
David Geffen School of Medicine at UCLA
Medicine and Physiology
47-123 CHS
Los Angeles, CA 90095
UNITED STATES
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| Work Address: |
Office
CHS 17-052
UNITED STATES
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Work Phone Number:
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(310) 206-2677
Office
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Technical Research Interest:
In embryogenesis, immature mesenchymal cells aggregate and
organize into patterned tissues. Later in life, a pathological
recapitulation of this process takes place in atherosclerotic
lesions, when vascular mesenchymal cells organize into trabecular
bone, cartilage and fat tissue within the artery wall. In
our laboratory, we developed a tissue culture model for this
process, and demonstrated that the ectopic tissue is formed
by mesenchymal stem cells present in the artery wall that
undergo abnormal lineage acquisition. We further showed that
these cells self-organize in vitro into patterns that are predicted
by a mathematical model based on molecular morphogens
interacting in a reaction-diffusion process governed by partial
differential equations. We identified the activator and inhibitor
morphogens as bone morphogenetic protein and its inhibitor,
matrix GLA protein (MGP). We confirmed the mathematical
model predictions in culture, showing that addition of MGP
alters the pattern from stripes to spots and showing that
addition of warfarin, which inhibits MGP, creates a doubling of
stripe density. Thus, reaction-diffusion principles may play a
significant role in pathological morphogenetic processes in the
adult. We are now growing these stem cells on carbon nanotubes
to attempt to modulate and refine the pattern formation
for future potential use in tissue reconstruction.
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Hoshino, T. Chow, L. A. Hsu, J. J. Perlowski, A. A. Abedin, M. Tobis, J. Tintut, Y. Mal, A. K. Klug, W. S. Demer, L. L. , Mechanical stress analysis of a rigid inclusion in distensible material: A model of atherosclerotic calcification and plaque vulnerability, Am J Physiol Heart Circ Physiol, 2009.
Hsu, J. J. Lu, J. Huang, M. S. Geng, Y. Sage, A. P. Bradley, M. N. Tontonoz, P. Demer, L. L. Tintut, Y. , T0901317, an LXR agonist, augments PKA-induced vascular cell calcification, FEBS Lett, 2009, 583 ( 8), 1344-8.
Demer, L. L. Tintut, Y. , A matter of degree: a commentary on "Influence of oxidized low-density lipoproteins (LDL) on the viability of osteoblastic cells", Free Radic Biol Med, 2008, 44 ( 4), 504-5.
Huang, M. S. Lu, J. Ivanov, Y. Sage, A. P. Tseng, W. Demer, L. L. Tintut, Y. , Hyperlipidemia impairs osteoanabolic effects of PTH, J Bone Miner Res, 2008, 23 ( 10), 1672-9.
Hsu, J. J. Tintut, Y. Demer, L. L. , Murine models of atherosclerotic calcification, Curr Drug Targets, 2008, 9 ( 3), 224-8.
Morony S, Tintut Y, Zhang Z, Cattley RC, Van G, Dwyer D, Stolina M, Kostenuik PJ, Demer LL, Osteoprotegerin inhibits vascular calcification without affecting atherosclerosis in ldlr((-/-)) mice, Circulation, 2008, 117 (3), 411-420.
Huang, M. S. Sage, A. P. Lu, J. Demer, L. L. Tintut, Y. , Phosphate and pyrophosphate mediate PKA-induced vascular cell calcification, Biochem Biophys Res Commun, 2008, 374 ( 3), 553-8.
Yochelis A, Tintut Y, Demer LL, Garfinkel A, The formation of labyrinths, spots and stripe patterns in a biochemical approach to cardiovascular calcification, New Journal of Physics , 2008, 10.
Demer, L. L. Tintut, Y. , Vascular calcification: pathobiology of a multifaceted disease, Circulation, 2008, 117 ( 22), 2938-48.
Hsu, J. J. Tintut, Y. Demer, L. L. , Vitamin D and osteogenic differentiation in the artery wall, Clin J Am Soc Nephrol, 2008, 3 ( 5), 1542-7.
Huang MS, Morony S, Lu JX, Zhang Z, Bezouglaia O, Tseng W, Tetradis S, Demer LL, Tintut Y, Atherogenic phospholipids attenuate osteogenic signaling by BMP-2 and parathyroid hormone in osteoblasts, Journal of Biological Chemistry, 2007, 282 (29), 21237-21243.
Jaffe IZ, Tintut Y, Newfell BG, Demer LL, Mendelsohn ME, Mineralocorticoid receptor activation promotes vascular cell calcification, ATVB, 2007, 27, 799-805.
Tintut, Y. Huang, M. Lu, J. Tseng, W. Garfinkel, A. Demer, L. L. , Vascular calcification, J Musculoskelet Neuronal Interact, 2007, 7 ( 4), 346.
Lin TC, Tintut Y, Rouhanizadeh M, Mack W, Demer LL, Hsiai TK, Mechanical response of a calcified plaque model to fluid shear force, Annals of Biomedical Engineering, 2006, 34 (10), 1535-41.
Abedin M, Lim J, Tang TB, Park D, Demer LL, Tintut Y, N-3 Fatty acids inhibit vascular calcification via the p38-MAPK and peroxisome proliferator-activated receptor-gamma pathways, Circulation Research, 2006.
Demer LL, Tintut Y, Pitting phosphate transport inhibitors against vascular calcification, Circulation Research, 2006.
Tintut Y, Morony S, Demer LL, Role of osteoprotegerin and its ligands and competing receptors in atherosclerotic calcification, Journal of Investigative Medicine, 2006.
Radcliff, K Tang, TB Lim, J Zhang, Z Abedin, M Demer, LL Tintut, Y, Insulin-like growth factor-I regulates proliferation and osteoblastic differentiation of calcifying vascular cells via extracellular signal-regulated protein kinase and phosphatidylinositol 3-kinase pathways, Circulation research, 2005, 96 (4), 398-400.
Tintut Y, Abedin M, Cho J, Choe A, Lim J, Demer L., Regulation of RANKL-induced osteoclastic differentiation by vascular cells, J Molec Cell Cardiol, 2005, 39 (2), 389-93.
Tintut, Y. Morony, S. Demer, L. L. , Hyperlipidemia promotes osteoclastic potential of bone marrow cells ex vivo, Arterioscler Thromb Vasc Biol, 2004, 24 ( 2), e6-10.
Abedin, M. Tintut, Y. Demer, L. L. , Mesenchymal stem cells and the artery wall, Circ Res, 2004, 95 ( 7), 671-6.
Hsiai, TK Cho, SK Wong, PK Ing, MH Salazar, A Hama, S Navab, M Demer, LL Ho, CM, Micro sensors: linking real-time oscillatory shear stress with vascular inflammatory responses, Annals of biomedical engineering, 2004, 32 (2), 189-201.
Garfinkel, A. Tintut, Y. Petrasek, D. Bostrom, K. Demer, L. L. , Pattern formation by vascular mesenchymal cells, Proc Natl Acad Sci U S A, 2004, 101 ( 25), 9247-50.
Demer LL, M Abedin, Skeleton key to vascular disease, J Amer Coll Cardiol, 2004, 44 (10), 1977-9.
Abedin, M. Tintut, Y. Demer, L. L. , Vascular calcification: mechanisms and clinical ramifications, Arterioscler Thromb Vasc Biol, 2004, 24 ( 7), 1161-70.
Demer, L. L. Tintut, Y. , Mineral exploration: search for the mechanism of vascular calcification and beyond: the 2003 Jeffrey M. Hoeg Award lecture, Arterioscler Thromb Vasc Biol, 2003, 23 ( 10), 1739-43.
Hsiai, TK Cho, SK Wong, PK Ing, M Salazar, A Sevanian, A Navab, M Demer, LL Ho, CM, Monocyte recruitment to endothelial cells in response to oscillatory shear stress, The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2003, 17 (12), 1648-57.
Tintut Y, Alfonso Z, Saini T, Radcliff K, Watson K, Bostrom K, Demer LL, Multilineage potential of cells from the artery wall, Circulation, 2003, 108, 2505-10.
Mody N, Demer LL, Vascular calcification and its relation to bone calcification: Possible underlying mechanisms, Journal of Nuclear Cardiology, 2003, 10, 177-83.
Tintut, Y Parhami, F Tsingotjidou, A Tetradis, S Territo, M Demer, LL, 8-Isoprostaglandin E2 enhances receptor-activated NFkappa B ligand (RANKL)-dependent osteoclastic potential of marrow hematopoietic precursors via the cAMP pathway, The Journal of biological chemistry, 2002, 277 (16), 14221-6.
Demer, LL, Adipose rex: Fat and fats that rule differentiation, Circulation Research, 2002, 90, 241-243.
Hsiai T, Cho SK, Honda H, Hama S, Navab M, Demer L, Ho CM, Endothelial cell dynamics under pulsating flows: Significance of high- vs. low shear stress slew rates (d(tau)/dt), Annals of Biomedical Engineering, 2002, 30, 646-56.
Parhami, F. Basseri, B. Hwang, J. Tintut, Y. Demer, L. L. , High-density lipoprotein regulates calcification of vascular cells, Circ Res, 2002, 91 ( 7), 570-6.
Tintut, Y. Patel, J. Territo, M. Saini, T. Parhami, F. Demer, L. L. , Monocyte/macrophage regulation of vascular calcification in vitro, Circulation, 2002, 105 ( 5), 650-5.
Demer, L. L. Tintut, Y. Parhami, F. , Novel mechanisms in accelerated vascular calcification in renal disease patients, Curr Opin Nephrol Hypertens, 2002, 11 ( 4), 437-43.
Parhami, F. Mody, N. Gharavi, N. Ballard, A. J. Tintut, Y. Demer, L. L. , Role of the cholesterol biosynthetic pathway in osteoblastic differentiation of marrow stromal cells, J Bone Miner Res, 2002, 17 ( 11), 1997-2003.
Demer, L. L. , Vascular calcification and osteoporosis: inflammatory responses to oxidized lipids, Int J Epidemiol, 2002, 31 ( 4), 737-41.
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