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Published byTiina Annikki Kivelä Modified over 6 years ago
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Potential pathological roles for oxidized low-density lipoprotein and scavenger receptors SR-AI, CD36, and LOX-1 in aortic valve stenosis Suvi Syväranta, Mervi Alanne-Kinnunen, Katariina Öörni, Riina Oksjoki, Markku Kupari, Petri T. Kovanen, Satu Helske-Suihko Atherosclerosis Volume 235, Issue 2, Pages (August 2014) DOI: /j.atherosclerosis Copyright © 2014 Elsevier Ireland Ltd Terms and Conditions
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Fig. 1 Expression of mRNA in aortic valve tissue from AVS patients and healthy controls. The expression levels of SR-A1 (A) and LOX-1 (D) are increased in AVS. There is a decrease in the expression of CD36 in stenotic valves (C), whereas the expression of SR-B1 remains constant (B). Results are presented as individual data points, lines indicate medians. Atherosclerosis , DOI: ( /j.atherosclerosis ) Copyright © 2014 Elsevier Ireland Ltd Terms and Conditions
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Fig. 2 Expression of mRNA in cultured aortic valve myofibroblasts (A–D, n = 4; E–F, n = 3; triplicates). Cells derived from stenotic aortic valves show increased expression of CD36 (C) and LOX-1 (D) when compared to control cells. The expression levels of SR-A1 (A) and SR-B1 (B) were similar in stenotic and control cells. LOX-1 expression was induced by mast cell releasate and TNF alpha in both stenotic cells (E and F) and in control cells (G and H). Results are presented as medians and interquartile ranges (A–D), and mean + SEM (E–H). Dots represent statistical outliers. Atherosclerosis , DOI: ( /j.atherosclerosis ) Copyright © 2014 Elsevier Ireland Ltd Terms and Conditions
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Fig. 3 Immunohistochemical distribution of scavenger receptors SR-A1, CD36 and LOX-1 in control and stenotic valves. A and B, SR-A1-positive cells are present in both control and stenotic valves. C, CD36 is confined to endothelial cells lining the control valve. D, In stenotic valves, CD36 is also present in vascular structures. E and F, LOX-1 is absent from the control valve, but visible in parts of the endothelium lining the stenotic valve. The endothelial layer facing upwards represents the ventricular side of the leaflet, except for Fig. 3D, in which neovessels reside more centrally in the fibrotic valve tissue. Atherosclerosis , DOI: ( /j.atherosclerosis ) Copyright © 2014 Elsevier Ireland Ltd Terms and Conditions
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Fig. 4 Double immunofluorescence stainings of stenotic aortic valves. Arrows indicate colocalization, and asterisks denote the lumens of cross-sectional neovessels. A–C, SR-A1 confines to CD68-positive macrophages. D–F, a sporadic alpha actin-positive myofibroblast is also CD36-positive. G–L, LOX-1 colocalizes with CD31 and CD34-positive endothelial cells lining the valve (G–I), and also surrounds the endothelium of a vascular structure. Atherosclerosis , DOI: ( /j.atherosclerosis ) Copyright © 2014 Elsevier Ireland Ltd Terms and Conditions
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Fig. 5 Effects of oxLDL on cultured aortic valve myofibroblasts. A–E, The secretion of MCP-1 (A), IL-6 (B), M-CSF (C), and IL-8 (D) into cell culture media by myofibroblasts derived from a stenotic valve increased in response to oxLDL, whereas the mRNA expression of osteoprotegerin (OPG) decreased (E). F, In myofibroblasts derived from control valves, OxLDL increased the production of MCP-1, but the minor changes in IL-6 and IL-8 production remained statistically insignificant. Results are representative of 2 independent experiments, and presented as mean + SEM. Atherosclerosis , DOI: ( /j.atherosclerosis ) Copyright © 2014 Elsevier Ireland Ltd Terms and Conditions
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Fig. 6 A and B, Confocal microscopy images demonstrate a stronger intracellular signal from DiI-labeled oxLDL in a typical myofibroblast derived from a stenotic valve as compared to a typical myofibroblast from a control valve. C, Fluorometric analyses of three independent experiments (n = 3, triplicates) show that myofibroblasts from stenotic aortic valves take up more oxLDL than myofibroblasts from control valves. D, OxLDL uptake by myofibroblasts derived from control valves (n = 2, triplicates) increased significantly when the cells were pretreated with mast cell releasate or TNF alpha. Results are presented as medians and interquartile ranges. The dot represents a statistical outlier. Atherosclerosis , DOI: ( /j.atherosclerosis ) Copyright © 2014 Elsevier Ireland Ltd Terms and Conditions
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