Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1

Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease

Chronic Respiratory Failure in Neonates

The original publication on bronchopulmonary dysplasia (BPD) by Northway and collaborators described a group of preterm infants who after prolonged mechanical ventilation developed chronic respiratory failure and characteristic radiographic findings (Northway et al. 1967). The lung damage was attributed primarily to the use of aggressive positive-pressure ventilation and high inspired oxygen concentrations. Today, with the widespread use of antenatal corticosteroids and the use of postnatal surfactant and less aggressive mechanical ventilation, this severe form of BPD has been replaced by a milder form that presents in the more immature infants who frequently have only mild initial respiratory disease (Charafeddine et al. 1999; Parker et al. 1992; Rojas et al. 1995). Therefore, these infants are not exposed to the very high airway pressures or oxygen concentrations, the two main factors in the pathogenesis of the original form of BPD. This milder form of the disease has been described as “New BPD.” This new presentation has created some inconsistencies and confusion in the definition and the diagnostic criteria of BPD (Bancalari et al. 2003)