The pathogenic role of tumor necrosis factor superfamily ligands in atherogenesis and plaque destabilization
Year: 2008
Type: dissertation
Study design: Observational Study
Abstract: The aim of this thesis was to identify novel inflammatory mediators potentially contributing to plaque destabilization focusing on members of the tumor necrosis factor superfamily (TNFSF). 40 patients with stable angina, 40 patients with unstable angina and 20 healthy controls were investigated. Plasma levels of APRIL, LIGHT and OPG, all members of the TNFSF, was significantly raised in angina patients relative to controls with particularly high levels in unstable disease. Further studies pointed out T cells and/or monocytes as possible sources for the raised plasma levels of these mediators, and for APRIL, activated platelets seem to be the major contributor. To elucidate potential pathogenic effects of these TNFSF members, in vitro experiments were performed on cells with relevance to atherogenesis, revealing several pro-atherogenic effects, such as enhanced lipid accumulation in macrophages, inflammatory responses in endothelial cells, enhanced matrix degrading potential in vascular smooth muscle cells, and increased expression of pro-thrombotic mediators in macrophages. Immunostaining localized these TNFSF members to atherosclerotic plaques, supporting their atherogenic contribution.
Author: Wiggo J. Sandberg
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2400470920