Regulation of myosin light chain phosphatase and pulmonary arterial relaxation

Abstract

Neonatal circulatory transition is dependent upon tightly regulated pulmonary circuit relaxation. Persistent pulmonary hypertension (PPHN), a rapidly progressive disease of pulmonary arterial vasospasm and remodelling, may be characterized by pulmonary arterial myocyte relaxation failure. A key regulator of vascular tone is myocyte calcium sensitivity, determined by the relative stoichiometry of myosin light chain phosphorylation and dephosphorylation. We have recently reported downregulation of myosin light chain phosphatase activity in a hypoxic model of neonatal pulmonary hypertension. This review examines the recognized pathways of regulation governing myosin light chain phosphatase activity, including targeting subunit isoform switching, targeting unit phosphorylation and catalytic site inhibition. In light of the reviewed literature, further speculation is proposed on the potential contributions of these mechanisms to the pathophysiology of the perinatal pulmonary arterial relaxation defect in PPHN.Key words: smooth muscle, pulmonary hypertension, myosin light chain phosphatase, CPI-17, MYPT, review.