Age-related arterial dysfunction and gut dysbiosis in mice and cetaceans
Cardiovascular disease (CVD) is the number one cause of death in Europe. Arterial dysfunction develops with aging making advancing age the primary risk factor for CVD. Advancing age can induce adverse changes in the gut microbiome, which in turn, can activate systemic pro-oxidant and pro-inflammatory signaling pathways with detrimental downstream consequences. One main objective of this project is to investigate the role of the gut microbiome in modulating arterial function with aging. To approach this objective, I will carry out two experimental studies: 1) mouse-to mouse transplant of gut microbiota to investigate if gut microbiota transfers vascular phenotypes. This experiment will show if gut microbiota modulates arterial function with aging, and will provide insight into the mechanisms involved. 2) Germ-free mice with microbiota samples from human subjects to determine the contribution of the human microbiome to a particular phenotype. Cetaceans are long-lived mammals and excellent divers. They undergo constant cycles of tissue hypoxia-reoxygenation and shear stress caused by vascular adjustments while diving. In humans, these adjustments produce an elevation of oxidative stress and inflammation markers and impairment of the endothelial function. Thus, another main objective of this proposal is to explore if cetaceans, i.e. whales and dolphins, have developed an endothelium-protective mechanism to prevent arterial dysfunction with age and diving. To approach this objective I will study vascular function, circulating oxidative stress and inflammation markers, and gut microbiome of cetaceans of different ages in captivity as well as stranded animals.The objectives to investigate the role of the gut microbiome in modulating arterial function with aging will be carried during the first two years in the outgoing phase. This knowledge will be transfer to the host institution for the study of vascular function and gut microbiome in cetaceans of different ages.