Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
SHR
Neuro
Krebs
Kardio
Stoffw
Microb
Lipid
MPO-modifiziertes High-Density Lipoprotein und Rezeptoren
- Abstract
- The vascular endothelium is a wide spread organ responsible for the regulation of hemodynamics, angiogenic vascular remodeling, metabolic, synthetic, antiinflammatory, and antithrombogenic processes. Diminished nitric oxide (NO) availability has been linked to vascular disease and a heightened state of inflammation is characterized, in part, by an increase in vascular myeloperoxidase and proteins in vivo modified by its principal oxidant, hypochlourous acid/hypochlorous acid/hypochlorite (HOCI/OCI). Modification of high-density lipoprotein (HDL) by HOCI generates a proatherogenic and proinflammatory lipoprotein particle. HOCI-HDL, present in human lesions material and on endothelial cells, attenuates the expression and activity of vasuloprotective endothelial NO synthase (eNOS). Therefore, one part of this application is to clarify the mechanisms that governs interaction of HODI-HDL and its lipid (plasmalogen)-derived oxidant 2-chlorohexadecanal with eNOS, to focus whether caveolae-located proteins are involved, to profile alterations in endothelial gene expression patterns, and to investigate endothelium-dependent vascular relaxation in aortic rings and perfused vessels. As endothelial dysfunction may be induced by receptor-ligand interaction, the other part of this application will focus on interaction of HOCI-HDL with candidate receptors mediating (patho)physiologically relevant cellualar responses, i.e. activation of transcription factors, kinases and production of cytokines, leadng to the perpetuation of the inflammatory response and endothelial dysfunction. To answer these questions cell lines overexpressing candidate receptors will be used before adapting the cellular signaling cascade patterns to a specific endothelial cell line. We propose that myeloperoxidase-modified HDL- a unique and clinically significant marker for atherosclerosis - mediates endothelial dysfunction by specific receptor-evoked intracellular signaling pathways.
- Schlagworte
- Medizinische Biochemie
- Medizinische Molekularbiologie
- Strahlentherapie
- (High-density) lipoprotein
- Hypochlorite
- Hypochlorous acid
- Myeloperoxidase
- NO biosynthesis
- Scavenger Receptors
- Projektleitung:
- Malle Ernst
- Laufzeit:
- 16.12.2006-15.12.2011
- Programm:
- FWF Einzelprojekt
- Art der Forschung
- Grundlagenforschung
- Mitarbeiter*innen
- Malle, Ernst, Projektleiter*in
- Beteiligte MUG-Organisationseinheiten
- Lehrstuhl für Molekularbiologie und Biochemie
- Gefördert durch
- FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Österreich
FWF-Grant-DOI: 10.55776/P19074
- Publizierte Projektergebnisse
- > LPA-induced suppression of periostin in human oste... Biochimie. 2012; 94(9):1997-2005
- > Phloretin ameliorates 2-chlorohexadecanal-mediated... Free Radic Biol Med. 2012; 53(9):1770-1781
- > Targeted subendothelial matrix oxidation by myelop... Free Radic Biol Med. 2012; 53(12):2344-2356
- > Hypochlorite-modified low-density lipoprotein indu... Biochem Biophys Res Commun. 2011; 410(4): 895-900.
- > Hypochlorite-modified high-density lipoprotein pro... Arch Biochem Biophys. 2011; 509(1):16-25
- > Neutrophil-cytokine interactions in a rat model of... TOXICOLOGY. 2011; 290(2-3): 278-285.
- > Peroxynitrite modifies the structure and function ... FREE RADICAL BIOL MED. 2010; 49(2): 282-293.