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470 results on '"Demer, Linda L"'

101. Runx2-Upregulated Receptor Activator of Nuclear Factor κB Ligand in Calcifying Smooth Muscle Cells Promotes Migration and Osteoclastic Differentiation of Macrophages

Author

Byon, Chang Hyun, primary, Sun, Yong, additional, Chen, Jianfeng, additional, Yuan, Kaiyu, additional, Mao, Xia, additional, Heath, Jack M., additional, Anderson, Peter G., additional, Tintut, Yin, additional, Demer, Linda L., additional, Wang, Deli, additional, and Chen, Yabing, additional

Published
2011
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141. Inflammation Drives Retraction, Stiffening, and Nodule Formation via Cytoskeletal Machinery in a Three-Dimensional Culture Model of Aortic Stenosis

Author

Lim, Jina, Ehsanipour, Arshia, Hsu, Jeffrey J., Lu, Jinxiu, Pedego, Taylor, Wu, Alexander, Walthers, Chris M., Demer, Linda L., Seidlits, Stephanie K., and Tintut, Yin

Abstract

In calcific aortic valve disease, the valve cusps undergo retraction, stiffening, and nodular calcification. The inflammatory cytokine, tumor necrosis factor (TNF)-α, contributes to valve disease progression; however, the mechanisms of its actions on cusp retraction and stiffening are unclear. We investigated effects of TNF-α on murine aortic valvular interstitial cells (VICs) within three-dimensional, free-floating, compliant, collagen hydrogels, simulating their natural substrate and biomechanics. TNF-α increased retraction (percentage of diameter), stiffness, and formation of macroscopic, nodular structures with calcification in the VIC-laden hydrogels. The effects of TNF-α were attenuated by blebbistatin inhibition of myosin II–mediated cytoskeletal contraction. Inhibition of actin polymerization with cytochalasin-D, but not inhibition of Rho kinase with Y27632, blocked TNF-α–induced retraction in three-dimensional VIC hydrogels, suggesting that actin stress fibers mediate TNF-α–induced effects. In the hydrogels, inhibitors of NF-κB blocked TNF-α–induced retraction, whereas simultaneous inhibition of c-Jun N-terminal kinase was required to block TNF-α–induced stiffness. TNF-α also significantly increased collagen deposition, as visualized by Masson's trichrome staining, and up-regulated mRNA expression of discoidin domain receptor tyrosine kinase 2, fibronectin, and α-smooth muscle actin. In human aortic valves, calcified cusps were stiffer and had more collagen deposition than noncalcified cusps. These findings suggest that inflammation, through stimulation of cytoskeletal contractile activity, may be responsible for valvular cusp retraction, stiffening, and formation of calcified nodules.

Published
2016
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142. Outcomes of a Novel Training Program for Physician-Scientists: Integrating Graduate Degree Training With Specialty Fellowship

Author

Wong, Mitchell D., Guerrero, Lourdes, Sallam, Tamer, Frank, Joy S., Fogelman, Alan M., and Demer, Linda L.

Abstract

ABSTRACTBackgroundAlthough physician-scientists generally contribute to the scientific enterprise by providing a breadth of knowledge complementary to that of other scientists, it is a challenge to recruit, train, and retain physicians in a research career pathway.Objective To assess the outcomes of a novel program that combines graduate coursework and research training with subspecialty fellowship.Methods A retrospective analysis was conducted of career outcomes for 123 physicians who graduated from the program during its first 20 years (1993–2013). Using curricula vitae, direct contact, and online confirmation, data were compiled on physicians' subsequent activities and careers as of 2013. Study outcomes included employment in academic and nonacademic research, academic clinical or private practice positions, and research grant funding.Results More than 80 of graduates were actively conducting research in academic, institutional, or industrial careers. The majority of graduates (71) had academic appointments; a few (20) were in private practice. Fifty percent had received career development awards, and 19 had received investigator-initiated National Institutes of Health (NIH) R01 or equivalent grants. Individuals who obtained a PhD during subspecialty training were significantly more likely to have major grant funding (NIH R series or equivalent) than those who obtained a Master of Science in Clinical Research. Trainees who obtained a PhD in a health services or health policy field were significantly more likely to have research appointments than those in basic science.Conclusions Incorporation of graduate degree research, at the level of specialty or subspecialty clinical training, is a promising approach to training and retaining physician-scientists.

Published
2016
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148. FGF23 protein expression in coronary arteries is associated with impaired kidney function.

Author

van Venrooij, Natalie A., Pereira, Renata C., Tintut, Yin, Fishbein, Michael C., Tumber, Navdeep, Demer, Linda L., Salusky, Isidro B., and Wesseling-Perry, Katherine

Subjects
PROTEIN expression, FIBROBLAST growth factors, CHRONIC kidney failure, KIDNEY physiology, CORONARY disease, IMMUNOHISTOCHEMISTRY, CALCIFICATION
Abstract

Background Fibroblast growth factor 23 (FGF23) levels are elevated in chronic kidney disease (CKD) and elevated values have been associated with both heart disease and mortality. Recent studies show that FGF23, a protein synthesized by osteocytes, is also present in calcified atherosclerotic plaques and may be induced by heart disease. Whether vascular expression of FGF23 is associated with progressive CKD, however, remains unknown. Therefore, the relationship between kidney function, vascular calcification and FGF23 expression was evaluated in patients with heart disease. Methods Immunohistochemistry for FGF23 was performed in coronary arteries of all patients undergoing heart transplantation at UCLA between February 2008 and 2010. Immunohistochemical staining for Klotho, DMP1, FGFR1, and FGFR3; calcium deposition; and RNA expression of Klotho and DMP1 were assessed in a subset of eight samples. Results FGF23 was detected by immunohistochemistry in 56% of the coronary artery specimens. Vascular FGF23 expression correlated with declining kidney function, as evidenced by reduced creatinine clearance. FGFR1 and FGFR3 were detected throughout the vascular tissue and in calcified plaques. Calcium deposition, Klotho expression and DMP1 expression correlated with FGF23 immunoreactivity. Conclusions The findings suggest that the Klotho-FGF23-FGFR system is active in coronary arteries and its upregulation correlates with impaired renal function and matrix calcium deposition. [ABSTRACT FROM PUBLISHER]

Published
2014
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149. Effects of bioactive lipids and lipoproteins on bone.

Author

Tintut, Yin and Demer, Linda L.

Subjects
*BIOACTIVE compounds, *LIPIDS, *LIPOPROTEINS, *BONE proteins, *ATHEROSCLEROTIC plaque, *VASCULAR diseases, *OSTEOBLASTS, *OSTEOCLASTS
Abstract

Highlights: [•] A link between atherosclerotic vascular disease and bone loss is discussed. [•] Lipids/lipoproteins have direct effects on the differentiation of osteoblasts and osteoclasts. [•] Lipids/lipoproteins blunt the bone anabolic effects of PTH (1–34). [•] Oxidant stress plays a role in hyperlipidemic bone disease. [Copyright &y& Elsevier]

Published
2014
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