Link: https://www.ncbi.nlm.nih.gov/pubmed/30759452

Pediatr Res. 2019 Feb 13. doi: 10.1038/s41390-019-0335-6. [Epub ahead of print]
MIF inhibition enhances pulmonary angiogenesis and lung development in congenital diaphragmatic hernia.
Perveen S1, Ayyasola K2, Zagloul N2, Patel H2, Ochani K3, Orner D2, Benveniste H4, Salerno M5, Vaska P5,6, Zuo Z7, Alabed Y8, Nasim M9, Miller EJ3, Ahmed M2.
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Abstract
BACKGROUND:
Congenital diaphragmatic hernia (CDH) is a complex birth anomaly with significant mortality and morbidity. Lung hypoplasia and persistent pulmonary hypertension (PPHN) limit survival in CDH. Macrophage migration inhibitory factor (MIF), a key regulator of innate immunity, is involved in hypoxia-induced vascular remodeling and PPHN. We hypothesized that antenatal inhibition of MIF in CDH fetuses, would reduce vascular remodeling, and improve angiogenesis and lung development.

METHODS:
Pregnant rats were randomized into three groups: Control, nitrofen, and nitrofen + ISO-92. Lung volumes of pups were measured by CT scanning. Right ventricular systolic pressure (RVSP) and vascular wall thickness (VWT) were measured together with MIF concentration, angiogenesis markers, lung morphometry, and histology.

RESULTS:
Prenatal treatment with ISO-92, an MIF inhibitor, improved normalization of static lung volume, lung volume-to-body weight ratio, decreased alveolar septal thickness, RVSP and VWT and improved radial alveolar count as compared to the non-treated group. Expression of MIF was unaffected by ISO-92; however, ISO-92 increased p-eNOS and VEGF activities and reduced arginase 1, 2 and Sflt-1.

CONCLUSION:
Prenatal inhibition of MIF activity in CDH rat model improves angiogenesis and lung development. This selective intervention may be a future therapeutic strategy to reduce the morbidity and mortality of this devastating condition.

PMID: 30759452 DOI: 10.1038/s41390-019-0335-6