Obiettivo The role of p27 on human atherosclerosis and the interplay between ROS and cell cycle control within the arterial wall will be addressed. - A) Single nucleotide polymorphisms (SNPs) within the promoter region of the p2 7 gene will be identified using DNA samples from 200 patients who survived after myocardial infarction and 200 contraols. VSMCs cultures will be transfected with plasmids in which reporter gene expression is under the controls of the p27 gene promoter containing the different SNPs. Luciferase activity of each SNP will indicate its relative transcriptional activity. To assess whether p27 SNPs are linked to increased risk of coronary disease, the frequency of each SNP will be determined in a sample of approximately 500 patients with premature heart disease and 500 healthy control individuals. Statistical analyses will be carried out to determine if altered levels of p27 due to SNPs in the promoter region of the gene are associated with increased risk of human cardiovascular disease. -B) Does oxidative stress influence atherogenesis when different levels of p27 protein are expressed? Doubly-deficient ecSOD-/- and apoE-:- mice will be generated. These mice will be mated with mice lacking p27 and the kinetics of experimental atherosclerosis after receiving a high-fat diet will be studied. Campo scientifico natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health scienceshealth sciencesnutritionnatural sciencesbiological sciencesgeneticsnucleotides Programma(i) FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002) Argomento(i) Data not available Invito a presentare proposte Data not available Meccanismo di finanziamento RGI - Research grants (individual fellowships) Coordinatore CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS Contributo UE Nessun dato Indirizzo Jaime Roig 11 46010 VALENCIA Spagna Mostra sulla mappa Costo totale Nessun dato