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The insulin-like growth factor (IGF) system is the dominant endocrine regulator of fetal growth, whereas insulin has a permissive role. Although a role for leptin in fetal growth has been suggested recently, the mechanism by which leptin may be related to fetal growth is not known; but leptin may interact with the IGF system in utero as it does in the(More)
We investigated the role of heme oxygenase (HO)-1 in the development of hypoxia-induced pulmonary hypertension. HO catalyzes the breakdown of heme to the antioxidant bilirubin and the vasodilator carbon monoxide. Hypoxia is a potent but transient inducer of HO-1 in vascular smooth muscle cells in vitro and in the lung in vivo. By using agonists of HO-1, we(More)
Regulation of fetal growth is multifactorial and complex. Diverse factors, including intrinsic fetal conditions as well as maternal and environmental factors, can lead to intrauterine growth restriction (IUGR). The interaction of these factors governs the partitioning of nutrients and rate of fetal cellular proliferation and maturation. Although IUGR is(More)
OBJECTIVE We previously reported improved oxygenation, but no change, in rates of extracorporeal membrane oxygenation (ECMO) use or death among infants with persistent pulmonary hypertension of the newborn who received inhaled nitric oxide (NO) with conventional ventilation, irrespective of lung disease. The goal of our study was to determine whether(More)
Vascular endothelial growth factor (VEGF) is a potent mitogenic and permeability factor targeting predominantly endothelial cells. At least two tyrosine kinase receptors, Flk-1 and Flt-1, mediate its action and are mostly expressed by endothelial cells. VEGF and VEGF receptor expression are upregulated by hypoxia in vivo and the role of VEGF in(More)
Extracellular acidosis (EA) has profound effects on vascular homeostasis, including vascular bed-specific alterations in vascular tone. Regulation of gene expression by EA has been observed in a variety of cells including vascular endothelial cells. Whether EA regulates gene expression in vascular smooth muscle cells (VSMCs) is not known. Heme oxygenase(More)
INTRODUCTION Cell-free plasma hemoglobin is associated with poor outcome in patients with sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma protein that binds heme with extraordinary affinity, blocks these effects and has been proposed(More)
BACKGROUND Risk factors for maternal vitamin D deficiency and preterm birth overlap, but the distribution of 25-hydroxyvitamin D (25(OH)D) levels among preterm infants is not known. We aimed to determine the associations between 25(OH)D levels and gestational age. METHODS We measured umbilical cord plasma levels of 25(OH)D from 471 infants born at Brigham(More)
BACKGROUND Irisin is a novel myokine, secreted from skeletal muscle after exercise. Irisin mediates exercise-related energy expenditure by turning white adipose tissue (WAT) into brown adipose tissue (BAT). Thus, irisin is considered as a potential biomarker for obesity and metabolic syndrome. Infants born small for gestational age (SGA) have increased risk(More)
Heme oxygenase (HO) catalyzes the oxidation of heme to generate carbon monoxide (CO) and bilirubin. CO increases cellular levels of cGMP, which regulates vascular tone and smooth muscle development. Bilirubin is a potent antioxidant. Hypoxia increases expression of the inducible HO isoform (HO-1) but not the constitutive isoform (HO-2). To determine whether(More)