Get the PICTURE: PIn1 pathway as a target to prevent Chronic Thromboembolic pUlmonary hypeRtEension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of pulmonary embolism (PE), characterized by fibrothrombotic material obliterating large pulmonary arteries. The disease is underdiagnosed and the treatment (high-risk surgery, angioplasty and drugs) is complex. There is an unmet need to identify patients at risk developing CTEPH after acute PE. Both pulmonary arterial smooth muscle and endothelial cells (PAECs) contribute to the pathogenesis of CTEPH. Peptidyl-Prolyl Cis/Trans Isomerase NIMA-Interacting protein 1 (Pin1) displays pro-coagulant activity and its inhibition attenuates vascular cell dysfunction in vitro, and reduces vascular remodelling in vivo. Knowing that Pin1 levels are elevated in PAECs and plasma from CTEPH patients, we hypothesized that Pin1 is a potential predictive biomarker and its inhibition could be beneficial for the prevention of CTEPH. We consequently aim to investigate whether Pin1 is a discriminating biomarker to identify individuals at risk using large and unique cohorts of healthy subjects, acute PE and CTEPH patients. In addition, our goal is to explore whether inhibition of Pin1 could restore pulmonary vascular cell function using vessel/thrombosis on a-chip methodology coupled to live imaging and prevent CTEPH progression in vivo using a reliable animal model and imaging. The final goal is to translate our findings to the clinical practice to develop preventive therapeutic strategies to hinder CTEPH progression