This study recognizes the substantial value of lung tissue obtained from explanted lungs for fundamental research purposes.By analyzing pulmonary tissue affected by pulmonary hypertension, it is possible to discover shared pathogenetic mechanisms between these two groups and to gain a deeper understanding of the mechanisms underlying pulmonary hypertension.

Lung transplantation serves as the sole therapeutic approach targeting the enhancement of life expectancy and quality of life for individuals afflicted with advanced parenchymal or vascular lung diseases. The current study aligns with this objective, recognizing the substantial value of lung tissue obtained from explanted lungs for fundamental research purposes. By investigating lung tissue affected by both group 3 and group 1 pulmonary hypertension, it becomes possible to uncover shared pathogenic mechanisms between these two groups and gain a more profound understanding of the underlying mechanisms driving group 3 pulmonary hypertension. Furthermore, delving into the cells responsible for the expression of dysregulated miRNAs offers the potential to identify novel target mechanisms for the clinical management of group 3 pulmonary hypertension, an area currently limited in therapeutic options. Through a comparative analysis of the quantitative expression patterns of each miRNA among distinct groups, it becomes feasible to determine the extent of involvement of specific pathogenic pathways in the various forms of pulmonary hypertension. Consequently, this approach provides guidance for future research, directing focus towards the most relevant mechanisms of interest.

Inclusion criteria

• Patients who underwent lung transplantation at the AOU IRCCS Policlinico Sant'Orsola in Bologna and the IRCCS Fondazione Policlinico San Matteo in Pavia (satellite center) from January 1, 2010, to December 31, 2021.
• Diagnosis of idiopathic pulmonary arterial hypertension, idiopathic pulmonary fibrosis, or chronic obstructive pulmonary disease.
• Patients who underwent at least one pre-transplant right heart catheterization in clinically stable conditions, with findings of mPAP ≥ 25 mmHg, PVR > 3 WU, and PCP < 15 mmHg.
• Suitability of lung explant tissue available in the archives of the participating pathology departments: presence of at least 3 pulmonary arterioles in each specimen.
• Acquisition of informed consent. Exclusion criteria
• Unsuitability of lung tissue for molecular biology investigations (due to preservation issues or deterioration of the necessary arteriolar structures).
• Patients with active neoplastic diseases.

Tissue samples from lung explants of patients who underwent lung transplantation at IRCCS University Hospital of Bologna and at IRCCS San Matteo Hospital of Pavia from the 1st of January 2010 to the 31th of December 2021 were considered. Among 149 transplant performed in the two transplant center during the period of interest, we included in this study 27 patients who were submitted to single or double lung transplant with the following indications: idiopathic pulmonary arterial hypertension and idiopathic pulmonary fibrosis, or chronic obstructive pulmonary disease, both complicated by pulmonary arterial hypertension (defined as PAPm ≥ 25 mmHg) All patients underwent right heart catheterization during pre-transplant screening and had explanted lung samples available for the study.