Sumario

ACKNOWLEDGMENTS PREFACE SUMMARY RESUMEN 1. INTRODUCTION 1.1. CARDIOVASCULAR DISEASE 1.2. CELL-DERIVED MICROPARTICLES 1.3. CONCLUDING REMARKS AND UNRESOLVED ISSUES REFERENCES 2. HYPOTHESIS AND OBJECTIVES 3. MATERIALS AND METHODS 3.1. STUDY DESIGN 3.2. CLINICAL STUDY POPULATIONS 3.3. BLOOD SAMPLING AND CLINICAL DETERMINATIONS 3.4. MICROPARTICLE ISOLATION 3.5. FLOW CYTOMETRY OF CIRCULATING MICROPARTICLES 3.6. FUNCTIONAL STUDIES 3.7. DIFFERENTIAL PROTEOMICS STUDIES 3.8. MICRORNA ANALYSIS 3.9. VALIDATION TECHNIQUES 3.10. IN SILICO BIOINFORMATIC ANALYSES 3.11. STATISTICAL ANALYSES REFERENCES 4. RESULTS Article 1. Circulating and platelet-derived microparticles In human blood enhance thrombosis on atherosclerotic plaques Article 2. Lipid-lowering therapy with statins reduces microparticles shedding from endothelium, platelets and inflammatory cells Article 3. Circulating CD45+/CD3+ lymphocyte-derived microparticles map lipid-rich atherosclerotic plaques in FH patients Article 4. High levels of TSP1+/CD142+ platelet-derived microparticles characterise young patients with high cardiovascular risk and subclinical atherosclerosis Article 5. Growing thrombi release increased levels of CD235a+ microparticles and decreased levels of activated platelet-derived microparticles. Validation in ST-elevation myocardial infarction patients Article 6. Circulating microparticle signature in coronary and peripheral blood of ST elevation myocardial infarction patients in relation to pain-to-PCI elapsed time Article 7. Microparticles from thrombin-induced platelets have a complex proteomic profile rich in prothrombotic components Article 8. Exosomal microRNA signature predicts future ischemic events in hypercholesterolemic patients 5. DISCUSSION 6. CONCLUSIONS