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. The main objective of this project is to investigate the role of the gut microbiome in modulating arterial function with aging.

Figure 1: Schematic representation of the goal of the study.

This objective will be approached through two experimental studies: 1) mouse-to mouse transplant of gut microbiota to determine 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.

Figure 2:  Overview of the experimental studies and expected results. Blue is young, and orange is gold.

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 key objective of this project 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, circulating oxidative stress and inflammation markers and gut microbiome of cetaceans of different ages in captivity as well as stranded animals will be studied.

Figure 3:  Overview of the observational study in cetaceans and expected results. Blue is young, and orange is gold.

This project is funded by the European Commission (H2020-MSCA-IF-2019): “Arterial Aging” ref#892267