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- Spanbroek, R, et al.
(author)
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Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis
- 2003
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 100:3, s. 1238-1243
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Journal article (peer-reviewed)abstract
- Oxidation products of low-density lipoproteins have been suggested to promote inflammation during atherogenesis, and reticulocyte-type 15-lipoxygenase has been implicated to mediate this oxidation. In addition, the 5-lipoxygenase cascade leads to formation of leukotrienes, which exhibit strong proinflammatory activities in cardiovascular tissues. Here, we studied both lipoxygenase pathways in human atherosclerosis. The 5-lipoxygenase pathway was abundantly expressed in arterial walls of patients afflicted with various lesion stages of atherosclerosis of the aorta and of coronary and carotid arteries. 5-lipoxygenase localized to macrophages, dendritic cells, foam cells, mast cells, and neutrophilic granulocytes, and the number of 5-lipoxygenase expressing cells markedly increased in advanced lesions. By contrast, reticulocyte-type 15-lipoxygenase was expressed at levels that were several orders of magnitude lower than 5-lipoxygenase in both normal and diseased arteries, and its expression could not be related to lesion pathology. Our data support a model of atherogenesis in which 5-lipoxygenase cascade-dependent inflammatory circuits consisting of several leukocyte lineages and arterial wall cells evolve within the blood vessel wall during critical stages of lesion development. They raise the possibility that antileukotriene drugs may be an effective treatment regimen in late-stage disease.
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| 3. |
- Jostarndt, K, et al.
(author)
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Dissociation of apoptosis induction and CD36 upregulation by enzymatically modified low-density lipoprotein in monocytic cells
- 2002
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In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 290:3, s. 988-993
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Journal article (peer-reviewed)abstract
- Modified low-density lipoprotein (LDL) has been implicated as an initiating or amplifying factor in atherogenesis. Some of its biological activities, such as apoptosis induction and upregulation of the scavenger receptor CD36, appear to share common signaling pathways in cells of the cardiovascular system. Exposure of low-differentiated monocytic cells to LDL modified with 15-lipoxygenase and secretory phospholipase A(2) induced apoptosis and upregulated CD36. Cell treatment with constituents of modified LDL, such as 13-hydroxyoctadecadienoic acid (13-HODE), 25-hydroxycholesterol, and lysophosphatidyl choline, and with an unrelated apoptogen (TNF-related apoptosis-inducing ligand) induced apoptosis. In contrast, only 13-HODE caused upregulation of CD36 expression. Cotreatment with the pan-caspase inhibitor z.VAD-fmk resulted in suppression of apoptosis, but was without any effect on CD36 expression. These data indicate that in monocytic cells enzymatically modified LDL is capable of inducing both apoptosis and upregulation of CD36 expression. However, in our cellular model, the two induction processes appear to be causally unrelated. (C) 2002 Elsevier Science (USA).
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| 4. |
- Jostarndt, K, et al.
(author)
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Enzymatically modified low-density lipoprotein upregulates CD36 in low-differentiated monocytic cells in a peroxisome proliferator-activated receptor-γ-dependent way
- 2004
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In: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839. ; 67:5, s. 841-854
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Journal article (peer-reviewed)abstract
- Peroxisome proliferator-activated receptor-γ (PPARγ) has been suggested to upregulate CD36. Since free oxidized polyunsaturated fatty acids are PPARγ ligands, we studied the effects of LDL modified by the simultaneous action of sPLA2 and 15-lipoxygenase (15LO) on CD36 expression and PPARγ activation in monocytic cells. Exposure of MM6 cells, which do not express CD36 or other scavenger receptors, to such enzymatically modified LDL (enzLDL) resulted in upregulation of CD36 surface protein and mRNA expression. Similar effects were observed with free 13-hydroperoxyoctadecadienoic acid but not its esterified counterpart. Less pronounced effects were observed with LDL modified by 15LO alone. Upregulation of CD36 was inversely correlated to the state of cell differentiation, as showed by lower response to enzLDL of the scavenger receptor-expressing MM6-sr and THP1 cells. Importantly, LDL modified by sPLA2 and 15LO did not efficiently induce upregulation CD36 in PPARγ-deficient macrophage-differentiated embryonic stem cells confirming a role of PPARγ in CD36 expression in cells stimulated with enzLDL. Our data show that LDL modified with physiologically relevant enzymes stimulates CD36 expression in non-differentiated monocytes and that this process involves PPARγ activation. These effects of enzLDL can be considered pro-atherogenic in the context of early atherosclerosis.
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| 5. |
- Kasic, A., et al.
(author)
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Phonons and free-carrier properties of binary, ternary, and quaternary group-III nitride layers measured by infrared Spectroscopic Ellipsometry
- 2003
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In: Physica Status Solidi. C, Current topics in solid state physics. - : Wiley. - 1610-1634 .- 1610-1642. ; 0:6 SPEC. ISS., s. 1750-1769
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Conference paper (other academic/artistic)abstract
- This work reviews recent ellipsometric investigations of the infrared dielectric functions of binary, ternary, and quaternary group-III nitride films. Spectroscopic Ellipsometry in the mid-infrared range is employed for the first time to determine phonon and free-carrier properties of individual group-III nitride heterostructure components, including layers of some ten nanometer thickness. Assuming the effective carrier mass, the free-carrier concentration and mobility parameters can be quantified upon model analysis of the infrared dielectric function. In combination with Hall-effect measurements, the effective carrier masses for wurtzite n- and p-type GaN and n-type InN are obtained. The mode behavior of both the E1(TO) and A1(LO) phonons are determined for ternary compounds. For strain-sensitive phonon modes, the composition and strain dependences of the phonon frequencies are differentiated and quantified. Information on the crystal quality and compositional homogeneity of the films can be extracted from the phonon mode broadening parameters. A comprehensive IR dielectric function database of group-III nitride materials has been established and can be used for the analysis of complex thin-film heterostructures designed for optoelectronic device applications. Information on concentration and mobility of free carriers, thickness, alloy composition, average strain state, and crystal quality of individual sample constituents can be derived. © 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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