Objetivo Musculoskeletal disorders, particularly to the muscle-tendon unit, are a major cause of occupational disability in the European Union. The link between high cholesterol and poor tendon function has recently been demonstrated by several groups. However, the underlying pathophysiology of this association remains unknown. Cholesterol is known to leave the circulation and accumulate in extracellular matrix through interactions between LDL and glycosaminoglycans (GAG). Tendons are GAG rich in the interfascicular matrix (IFM: a tendon structure facilitating collagen fascicle sliding and extension). One putative mechanism by which high cholesterol may impact tendon function is an accumulation of cholesterol and LDL in the IFM, impairing fascicle sliding and extension. In addition, LDL readily becomes oxidized (oxLDL) when entrapped in the extravascular space, and recent data demonstrates this negatively impacts tendon cell phenotype, altering normal gene expression. This proposal aims to enhance our understanding of hypercholesterolemia on tendon health; a highly under-researched area of significant clinical importance. It employs expertise in tissue mechanics and tendon cell biology available at the host and external institutes to probe the mechanisms linking high cholesterol and tendon pathophysiology. The underlying hypotheses are that in individuals with elevated total cholesterol and/or LDL, cholesterol accumulates with LDL in GAG-rich areas of tendon like the IFM, inhibiting tendon biomechanical function. This hypothesis will be explored using suitable laboratory models, allowing the reversibility of these changes and their impact on tendon adaptation and healing to be examined. The findings will have immediate implications for orthopedic sciences, preventative medicine and rehabilitation services, strategies and technology. They have the potential to improve quality of life and reduce the socio-economic costs associated with orthopedic and musculoskeletal diseases. Ámbito científico medical and health sciencesbasic medicinephysiologypathophysiologymedical and health sciencesclinical medicinephysiotherapynatural sciencesbiological sciencescell biology Programa(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Tema(s) MSCA-IF-2015-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF) Convocatoria de propuestas H2020-MSCA-IF-2015 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-GF - Global Fellowships Coordinador QUEEN MARY UNIVERSITY OF LONDON Aportación neta de la UEn € 237 349,80 Dirección 327 MILE END ROAD E1 4NS London Reino Unido Ver en el mapa Región London Inner London — East Tower Hamlets Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 237 349,80 Socios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo Socio Las organizaciones asociadas contribuyen a la aplicación de la acción, pero no firman el acuerdo de subvención. UNIVERSITY OF BRITISH COLUMBIA Canadá Aportación neta de la UEn € 0,00 Dirección AGRONOMY ROAD 102-6190 V6T1Z1 Vancouver Ver en el mapa Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 145 622,40