Cel Atherosclerosis is a chronic inflammatory response, clinically asymptomatic in the first decade. The deposition of lipids in arterial walls, due to the uptake of oxidized low density lipoproteins (oxLDL) by macrophages, causes blood flow restriction making cardiovascular diseases (CVD) a serious public health problem in EU countries. In oxLDL, oxidation of (phospho)lipids and proteins occurs, originating phospholipids-protein adducts by cross-linking reactions. Though phospholipid-protein adducts were identified in atherosclerotic plaques by immunoassays, their structural features were not yet described. It is known that smaller and denser (SD) oxLDL is more atherogenic, but the mechanism is yet unclear. Improved understanding of the pathology and potential therapies depends on molecular characterization of atherogenic LDL particles including the phospholipid-Apo B (PL-Apo B) adducts. To achieve this, mass spectrometry based strategies will be used to characterize PL-Apo B adducts in SD oxLDL from healthy and diseased clinical samples. The methodological approach will be developed in control LDL in vitro oxidized (HOCl, MPO, Me+H2O2) to determine the nature of PL-Apo B adducts formed, followed by biotinylation and separation by avidin magnetic beads of PL-Apo B adducts for optimization of PL-Apo B adducts isolation protocols with high specificity and sensitivity. Detection through MS strategies (MRM, CID) avoids time consuming analysis by a focused detection approach. Subsequently, the optimized approach will be applied to LDL from clinical samples in search of PL-Apo B adducts. The data from clinical samples will be scrutinized by chemometric techniques for discriminant ions prior to full characterization. This study will contribute to the molecular understanding of CVD pathology. The development of advanced methods for routine analysis will enable identification of new biomarkers for early clinical diagnosis. Dziedzina nauki medical and health scienceshealth sciencespublic healthmedical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosisnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinepathologynatural scienceschemical sciencesanalytical chemistrymass spectrometry Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2009-IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Zaproszenie do składania wniosków FP7-PEOPLE-2009-IEF Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IEF - Intra-European Fellowships (IEF) Koordynator ASTON UNIVERSITY Wkład UE € 173 240,80 Adres ASTON TRIANGLE B4 7ET Birmingham Zjednoczone Królestwo Zobacz na mapie Region West Midlands (England) West Midlands Birmingham Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Kevin O'reilly (Mr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Uczestnicy (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko UNIVERSITY OF STRATHCLYDE Zakończenie uczestnictwa Zjednoczone Królestwo Wkład UE Brak danych Adres Richmond Street 16 G1 1XQ Glasgow Zobacz na mapie Region Scotland West Central Scotland Glasgow City Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Martin Gregory (Mr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych