Project: The prognostic and therapeutic potential of mediators of vascular calcification in a human lung microvascular model of COVID-19
Challenge Space
Health - Dependence
Principal Investigator(s) and team names
Dr Keith Rochfort (PI); Dr Paul Buchanan (Co-PI); Ms Niamh Donnelly (PhD student)
Collaborating Institutions
School of Veterinary Medicine, University College Dublin
Funding Support
DCU School of Nursing, Psychotherapy and Community Health PhD studentship
Project start date
1 October, 2022
End date
31 December, 2026
Problem
COVID-19 is increasingly recognised as a disease with important vascular as well as respiratory consequences.
Damage to the pulmonary microvasculature can contribute to inflammation, endothelial dysfunction and disruption of normal vascular homeostasis, with emerging evidence suggesting that pathways associated with vascular calcification may also become dysregulated.
At the same time, common vascular stressors such as vaping could potentially exacerbate these responses, creating a need to understand how COVID-19-associated vascular injury interacts with additional environmental exposures.
Background
The pulmonary microvascular endothelium forms a critical interface between the circulation and lung tissue and is particularly vulnerable during severe respiratory disease.
Exposure to SARS-CoV-2 proteins can trigger endothelial dysfunction and inflammatory signalling, potentially promoting changes associated with pathological vascular remodelling and calcification.
Vaping represents an additional and increasingly relevant challenge to lung and vascular health, exposing cells to nicotine and other aerosol-derived chemicals. However, relatively little is known about whether vaping can influence or amplify the vascular changes associated with COVID-19, particularly pathways involved in calcification.
Solution
This project brings together expertise across the DCU Life Sciences Institute to investigate the mechanisms underlying COVID-19-associated vascular injury and calcification.
At its core are advanced, human-relevant models of the pulmonary microvasculature, designed to recreate key features of the vascular environment within the lung and provide a controlled platform for studying disease mechanisms. These models are being used to determine how SARS-CoV-2-associated injury disrupts endothelial function and drives pathways linked to pathological vascular calcification, while also exploring whether additional stressors, including vaping, can exacerbate these effects.
Building on these mechanistic studies, a dedicated therapeutic work package investigates agents with the potential to protect or restore vascular function, particularly in severe COVID-19. Collaboration with UCD further strengthens this translational component, supporting the evaluation of potential therapeutic strategies. Together, the work aims to identify prognostic markers of disease severity while uncovering new opportunities to target COVID-19-associated vascular complications.