Vital Roles of Gremlin-1 in Pulmonary Arterial Hypertension Induced by Systemic-to-Pulmonary Shunts.

Background Heterozygous mutation in BMP (bone morphogenetic protein) receptor 2 is rare, but BMP cascade suppression is common in congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH); however, the underling mechanism of BMP cascade suppression independent of BMP receptor 2 mutation is unknown. Methods and Results Pulmonary hypertensive status observed in CHD-PAH was surgically reproduced in rats. Gremlin-1 expression was increased, but BMP cascade was suppressed, in lungs from CHD-PAH patients and shunted rats, whereas shunt correction retarded these trends in rats.