About Access
I am a member of ACCESS | I am applying to ACCESS
Linda Demer, M.D., Ph.D.  
   
 
Affiliations
Vice Chair and Professor, Medicine
Professor, Physiology
Director, Electrocardiographic Laboratory, Graduate Medical Education
Co-Director, UCLA Specialty Training and Advanced Research (STAR) Program
Member, ACCESS Program: Dept. of Molecular, Cell & Integrative Physiology, California NanoSystems Institute

Education:
Certification Type: Award, AHA Jeffrey M. Hoeg Award
Award, Franklin D. Murphy, M.D.
Award, Royal College of Physicians of Edinburgh
Award
Medical Degree: M.D., Johns Hopkins University School of Medicine, 1983
Degree: Ph.D., The Johns Hopkins University School of Medicine, 1983
B.S., University of Arizona, 1977
Certifications:
Medical Board Certification: Cardiovascular Disease, American Board of Internal Medicine, 1989
Internal Medicine, American Board of Internal Medicine, 1986


Contact Information:
Work Email Address: ldemer@mednet.ucla.edu
Electrocardiographic Laboratory: (310) 825-7359 Information and referral
(310) 825-6301 ECG technician pager
Physiology: 310-206-5661 (Fax)
Mailing Address: David Geffen School of Medicine at UCLA
Medicine and Physiology
47-123 CHS
Los Angeles, CA 90095
UNITED STATES
Work Address: Office
CHS 17-052

UNITED STATES
ARR Papers: http://www.cnsi.ucla.edu/arr/personnel-papers?personnel_id=8724
Home Page: http://www.cardiology.med.ucla.edu/faculty/demercv.htm


Direct Contact Information:
Work Phone Number: (310) 206-2677 Office


Research Interest:
Biomineralization in inflammatory diseases

Vascular calcification was previously considered an end-stage, inevitable process caused by passive crystal precipitation in dying cells. However, it is now known to be a common clinical occurrence closely linked to atherosclerosis. My research group demonstrated that calcium deposits in the artery wall are associated with expression of bone morphogenetic protein (BMP-2), a potent embryonic bone differentiation factor, and that fully-formed bone, cartilage and even marrow develop in atherosclerotic arteries in vivo. These findings suggest that the process is regulated at the molecular level and that it recapitulates embryonic programs. To further study this process, we developed an in vitro model in which artery wall cells spontaneously undergo osteoblastic differentiation, tracking the same gene expression cascade characteristic of bone cells. We have isolated and cloned the cells that produce bone, cartilage and marrow tissue in the artery wall, and identified them as mesenchymal stem cells. We found that their differentiation is enhanced by exposure to oxidized lipids, such as isoprostanes, that are present in atherosclerotic lesions, as well as to inflammatory cytokines, thus accounting for the association of vascular calcification with atherosclerotic lesions and other chronic inflammatory processes. Our work took an interdisciplinary direction into bone biology, when we found that similar oxidized lipids are present in the walls of vessels in bone where they have the opposite effect, impairing bone mineralization and promoting resorption by osteoclastic cells, suggesting that lipid accumulation and inflammation in bone as well as vascular tissues may account for the occurrence of both vascular calcification and osteoporosis in the same patients. Artery wall calcification has significant health implications given the increased risk of heart attack with calcified coronaries, the growing incidence of calcified aortic stenosis, use of mineralization-promoting agents in older women, and the widespread supplementation of foods with vitamin D.


Technical Research Interest:
Biomineralization in inflammatory diseases

Vascular calcification was previously considered an end-stage, inevitable process caused by passive crystal precipitation in dying cells. However, it is now known to be a common clinical occurrence closely linked to atherosclerosis. My research group demonstrated that calcium deposits in the artery wall are associated with expression of bone morphogenetic protein (BMP-2), a potent embryonic bone differentiation factor, and that fully-formed bone, cartilage and even marrow develop in atherosclerotic arteries in vivo. These findings suggest that the process is regulated at the molecular level and that it recapitulates embryonic programs. To further study this process, we developed an in vitro model in which artery wall cells spontaneously undergo osteoblastic differentiation, tracking the same gene expression cascade characteristic of bone cells. We have isolated and cloned the cells that produce bone, cartilage and marrow tissue in the artery wall, and identified them as mesenchymal stem cells. We found that their differentiation is enhanced by exposure to oxidized lipids, such as isoprostanes, that are present in atherosclerotic lesions, as well as to inflammatory cytokines, thus accounting for the association of vascular calcification with atherosclerotic lesions and other chronic inflammatory processes. Our work took an interdisciplinary direction into bone biology, when we found that similar oxidized lipids are present in the walls of vessels in bone where they have the opposite effect, impairing bone mineralization and promoting resorption by osteoclastic cells, suggesting that lipid accumulation and inflammation in bone as well as vascular tissues may account for the occurrence of both vascular calcification and osteoporosis in the same patients. Artery wall calcification has significant health implications given the increased risk of heart attack with calcified coronaries, the growing incidence of calcified aortic stenosis, use of mineralization-promoting agents in older women, and the widespread supplementation of foods with vitamin D.


Publications:
Morony S (Morony, Sean), Tintut Y (Tintut, Yin), Zhang Z (Zhang, Zina), Cattley RC (Cattley, Russell C.), Van G (Van, Gwyneth), Dwyer D (Dwyer, Denise), Stolina M (Stolina, Marina), Kostenuik PJ (Kostenuik, Paul J.), Demer LL (Demer, Linda L.) Osteoprotegerin inhibits vascular calcification without affecting atherosclerosis in ldlr((-/-)) mice . Ciculation 2008; 117(3): 411-420.
Yochelis A (Yochelis, A.), Tintut Y (Tintut, Y.), Demer LL (Demer, L. L.), Garfinkel A (Garfinkel, A.) The formation of labyrinths, spots and stripe patterns in a biochemical approach to cardiovascular calcification . New Journal of Physics 2008; 10: .
Huang MS (Huang, Michael S.), Morony S (Morony, Sean), Lu JX (Lu, Jinxiu), Zhang Z (Zhang, Zina), Bezouglaia O (Bezouglaia, Olga), Tseng W (Tseng, Wendy), Tetradis S (Tetradis, Sotirios), Demer LL (Demer, Linda L.), Tintut Y (Tintut, Yin) Atherogenic phospholipids attenuate osteogenic signaling by BMP-2 and parathyroid hormone in osteoblasts. Journal of Biological Chemistry 2007; 282(29): 21237-21243.
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.
Demer LL, Tintut Y. Return to Ectopia: Stem cells in the artery wall. Arterioscler Thromb Vasc Biol 2005; 25(7): 1307-8.
Tintut Y, Morony S, Demer LL. Hyperlipidemia promotes osteoclastic potential of bone marrow cells ex vivo. Arterioscler Thromb Vasc Biol 2004; 24: 6-10.
Abedin M, Tintut Y, Demer LL Mesenchymal stem cells and the artery wall. Circulation Research 2004; 95: 671-676.
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. Pattern formation by vascular mesenchymal cells. Proc Nat Acad Sci USA 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. Vascular calcification: Mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol 2004; 95(7): 671-6.
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 flow: 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 LL High density lipoprotein regulates calcification of vascular cells. Circulation Research 2002; 91: 570-576.
Parhami F, Mody N, Gharavi N, Ballard AJ, Tintut Y, Demer LL Role of the cholesterol biosynthetic pathway in osteoblastic differentiation of marrow stromal cells. Journal of Bone and Mineral Research 2002; 17: 1997-2003.
Demer LL. Vascular calcification and osteoporosis: Inflammatory responses to oxidized lipids. International Journal of Epidemiology 2002; 31: 737-41.


The code and contents of http://www.uclaaccess.ucla.edu are ©2009 UCLA ACCESS. All rights reserved.