Molecular physiopathogenetic mechanisms and development of new potential therapeutic strategies in persistent pulmonary hypertension of the newborn

Giuseppe Distefano, Pietro Sciacca

Persistent pulmonary hypertension of the newborn (PPHN) is a cyanogenic plurifactorial disorder characterized by failed postnatal drop of pulmonary vascular resistance and maintenance of right-to-left shunt across ductus arteriosus and foramen ovale typical of intrauterine life. The pathogenesis of PPHN is very complex and can result from functional (vasoconstriction) or structural (arteriolar remodeling, reduced pulmonary vessels density) anomalies of pulmonary circulation. Etiopathogenetic factors heterogeneity can strongly condition therapeutical results and prognosis of PPHN that is particularly severe in organic forms that are usually refractory to selective pulmonary vasodilator therapy with inhaled nitric oxide. This paper reports the more recent acquisitions on molecular physiopathogenetic mechanisms underlying functional and structural forms of PPHN and illustrates the bases for adoption of new potential treatment strategies for organic PPHN. These strategies aim to reverse pulmonary vascular remodeling in PPHN with arteriolar smooth muscle hypertrophy and stimulate pulmonary vascular and alveolar growth in PPHN associated with lung hypoplasia.In order to restore lung growth in this severe form of PPHN, attention is focused on the results of studies of mesenchymal stem cells and their therapeutical paracrine effects on bronchopulmonry dysplasia, a chronic neonatal lung disease characterized by arrested vascular and alveolar growth and development of pulmonary hypertension.