Cellular senescence in vascular wall mesenchymal stromal cells, a possible contribution to the development of aortic aneurysm

Abstract

Cellular senescence is a hallmark of ageing and it plays a key role in the development of age-related diseases. Abdominal aortic aneurysm (AAA) is an age related degenerative vascular disorder, characterized by a progressive dilatation of the vascular wall and high risk of rupture over time. Nowadays, no pharmacological therapies are available and the understanding of the molecular mechanisms that lead to AAA onset and development are poorly defined.In this study we investigated the cellular features of senescence in vascular mesenchymal stromal cells, isolated from pathological (AAA – MSCs) and healthy (h – MSCs) segments of human abdominal aorta and their implication in impairing the vascular repair ability of MSCs.Cell proliferation, ROS production, cell surface area, the expression of cyclin dependent kinase inhibitors p21CIP1 and p16INK4a, the activation of the DNA damage response and a dysregulated autophagy showed a senescent state in AAA - MSCs compared to h-MSCs. Moreover, a reduced ability to differentiate toward endothelial cells was observed in AAA – MSCs.All these data suggest that the accumulation of senescent vascular MSCs over time impairs their remodeling ability during ageing. This condition could support the onset and development of AAA.