Cardiovascular and cerebrovascular diseases are the leading causes of death worldwide, particularly among elderly individuals, accounting for more than 20.5 million deaths in 2021 — close to a third of all deaths globally. As age-related cardiovascular and cerebrovascular diseases often stem from arterial stiffening and consequent alterations in arterial function, identifying a targeted therapy that specifically addresses the underlying mechanisms driving arterial stiffness is critical but currently lacking.
Importantly, an increase in blood vessel stiffness leads to significant changes in blood flow-induced forces (both pressure and shear stress) and impacts the arterial endothelium, which plays a central role in maintaining vascular integrity and homeostasis in response to hemodynamic forces.
However, the influence of layer-specific microscale mechanics on cellular function in cardiovascular diseases remains relatively understudied. To develop novel treatments for resolving pathological vascular aging and preventing age-related vascular pathologies, it is essential to understand the cellular and functional changes that occur in the vasculature during aging. One of the main challenges in developing new therapies for vascular aging is the limitation of existing preclinical models, mainly non-human animal models, to accurately mimic the dynamic remodelling seen in clinical settings.
Engineered models, specifically Organ-on-a-Chip models, are emerging as alternative tools for disease modelling, assessing cellular interactions, tissue regeneration and maturation, toxicology assays, and drug development. The overarching aim of this proposal is to overcome current limitations in understanding vascular aging and to find effective strategies to prevent pathological vascular aging.