Background: With an increasing percentage of
extremely immature infants surviving, cardiopulmonary complications have
become the most prevalent morbidity in this patient group. The
underlying pathology of vascular disease (PVD) in preterms with chronic
lung disease (BPD, bronchopulmonary dysplasia), associated with a high
risk for progression into pulmonary hypertension (PH), is only
incompletely understood and early, non-invasive biomarkers indicating
early-stage disease are missing.Methods and Results:
We prospectively included 190 preterm infants born <32 weeks
postmenstrual age in the AIRR (Attention to Infants at Respiratory
Risks) study (DRKS00004600) after informed parental consent.
Identification of pathologic pulmonary artery flow and right heart
strain by cardiopulmonary magnetic resonance imaging (MRI) at near-term
age enabled us to identify plasma markers associated with PVD early
after birth from proteomic screening. The differential regulation of
IL-7 and its receptor IL7R, observed together with markers known from
endothelial injury and remodeling , was confirmed by RNA scope analysis
in human lung tissue (Vanderbilt University) from preterms with and
without BPD and/or BPD-PH. Both vascular expression as well as cross
talk to distinct immune cell populations was observed. Analysis of
genetic data providing background information to this phenomenon is
ongoing.Conclusion: Showcasing the regulation
of IL-7R expression in infants with BPD indicates a role of IL7
signaling in PVD pathophysiology and outlines its potential as a disease
marker and future therapeutic target.