Air pollution as a CAtalyzer of defective angiogenesis Driving chronic thromboEmbolic pulMonary hypertension progression: Insights from in vivo and in vitro ApproachesAcronym: ACADEMIA

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of pulmonary embolism (PE). However, the absence of specific symptoms prevents or delays its diagnosis. Treatment is complex, involving high-risk surgery, angioplasty and drugs, and is not always efficient. There is a crucial need to understand why a subset of patients develop CTEPH after acute PE and to implement therapeutic strategy preventing the progression of CTEPH in patients at risk. Angiogenesis is known to contribute to the resolution of thrombo-emboli, and air pollution to worsen venous thromboembolism outcome. We consequently hypothesized that air pollution, by driving defective angiogenesis, could fasten progression of CTEPH. Our project aims to investigate whether air pollution driven defective angiogenesis contributes to progression of CTEPH, using i) patient material for the in vitro reconstitution of the epithelium-endothelium interface on a lung on-a-chip, and to model interactions of the endothelium with the extracellular matrix through a vessel on-a chip technology; and ii) in vivo, an existing reliable rabbit model of early CTEPH. If we are able to show that air pollution can worsen the course of CTEPH by driving defective angiogenesis and/or that pro-angiogenic factors can prevent CTEPH after acute PE, we ultimately aim to promote less invasive therapeutic, preventive and more cost-effective strategies, with reduced risk for patients and benefit for the healthcare system.

Keywords:thromboembolic pulmonary hypertension, ambient air pollution, angiogenesis, organ on-a-chip, gene therapy, pulmonary embolism, animal model

Disciplines:Vascular diseases, Cellular interactions and extracellular matrix, Pathophysiology, Respiratory medicine