Anti–sFlt-1 Therapy Preserves Lung Alveolar and Vascular Growth in Antenatal Models of Bronchopulmonary Dysplasia

Abstract

We conclude that treatment with anti-sFlt-1 mAb preserves lung structure and function and prevents right ventricular hypertrophy in two rat models of BPD of antenatal stress and speculate that early mAb therapy may provide a novel strategy for the prevention of BPD.

Chemical shift of 129Xe dissolved in red blood cells: Application to a rat model of bronchopulmonary dysplasia

“…Furthermore, an overall lower blood fraction was measured in the segmented images of the exposed cohort compared with the unexposed cohort (Figure A). The decreased blood fraction and proportional decrease in smaller RBC areas may be representative of stunted vascular development at the alveolar level that compromises response to hypoxia, previously shown to be a hallmark of BPD pathogenesis …”

“…The decreased blood fraction and proportional decrease in smaller RBC areas may be representative of stunted vascular development at the alveolar level that compromises response to hypoxia, previously shown to be a hallmark of BPD pathogenesis. 48,49 At low τ, the dissolved 129 Xe signal is restricted to the gas exchange region of the lungs while higher values of τ (i.e., τ > 500 ms) are long enough for the 129 Xe to transit into the larger vessels downstream of the lungs. 36 An interesting feature of the δ RBC versus τ curve is the upward slope at τ < 200 ms.…”

Fetal umbilical, cerebral and pulmonary blood flow patterns in relation to lung function and asthma in childhood. The Generation R Study

“…Children born with a very low birthweight or preterm are at higher risks of severe chronic respiratory diseases, such as bronchopulmonary dysplasia (BPD) . Intrauterine conditions such as abnormal placental flow or suboptimal development of the placenta may lead to an increased expression of angiogenic factors, such as soluble fms‐like tyrosine kinase‐1 and vascular endothelial growth factor, which increases the risk of chronic respiratory diseases in childhood . Also, an elevated inflammation status, found in growth restricted fetuses, could lead to reduced lung function later in life .…”

“…26 Intrauterine conditions such as abnormal placental flow or suboptimal development of the placenta may lead to an increased expression of angiogenic factors, such as soluble fms-like tyrosine kinase-1 and vascular endothelial growth factor, which increases the risk of chronic respiratory diseases in childhood. 27,28 Also, an elevated inflammation status, found in growth restricted fetuses, could lead to reduced lung function later in life. 29 Impaired vasculogenesis and angiogenesis, found in children with intrauterine growth restriction, might be other mechanisms than structural lung growth alterations leading to a suboptimal lung development.…”

Amelioration of muscular dystrophy phenotype in mdx mice by inhibition of Flt1

“…MAb-based therapeutics for the treatment of DMD have been developed to increase muscle mass via targeting myostatin and to decrease fibrosis via targeting fibroadipogenic progenitors (45). Further optimization using with humanized antibodies are required for future translation to humans (46). Taken together, we have gathered evidence for the first time that FLT1-targeted MAbs may be an effective therapeutic approach for the treatment of DMD.…”