Premature differentiation of vascular smooth muscle cells in human congenital diaphragmatic hernia |
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Authors: | Ilona Sluiter Irene van der Horst Paul van der Voorn Anne Boerema-de Munck Marjon Buscop-van Kempen Ronald de Krijger Dick Tibboel Irwin Reiss Robbert J Rottier |
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Institution: | 1. Department of Pediatric Surgery, Erasmus MC Rotterdam, The Netherlands;2. Department of Pathology, Erasmus MC Rotterdam, The Netherlands;3. Department of Cell Biology, Erasmus MC Rotterdam, The Netherlands |
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Abstract: | BackgroundCongenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterized by the herniation of abdominal organs into the chest cavity. The high mortality and morbidity of CDH patients are primarily caused by the associated pulmonary hypertension (PH), characterized by the thickening of the vascular media and adventitia. The media consist of heterogeneous populations of vascular smooth muscle cells (VSMC), ranging from synthetic to the characteristic contractile cells. VSMCs are influenced by developmental and environmental cues and may play a role in the development of the structural changes observed in CDH patients. Therefore, we hypothesized that the distribution of the VSMC populations may already be different at the origin of CDH development.MethodologyWe analyzed the protein expression of specific markers associated with synthetic and contractile VSMC phenotypes in human lungs at different developmental stages. Next, we compared lungs of premature and term CDH patients, as well as patients with lung hypoplasia due to renal agenesis or PROM, with age-matched controls.ResultsSynthetic and contractile VSMCs are distributed in a temporal and spatial specific pattern along the proximodistal axis of the lung. CDH patients have more abundant contractile VSMCs which are also more distally distributed. This different distribution pattern is already observed from 19 weeks of gestation onwards.ConclusionOur data suggest that the more extensive distribution of contractile VSMCs is associated with an early maturation of the pulmonary vasculature, contrasting the concept that CDH might be the result of delayed maturation of the epithelium. |
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Keywords: | α-SMA alpha smooth muscle actin CDH congenital diaphragmatic hernia CRBP1 cellular retinol binding protein ECMO extra corporeal membrane oxygenation MYL-9 myosin regulatory light chain 9 PH pulmonary hypertension PROM premature rupture of membranes RA retinoic acid SM-MHC smooth muscle myosin heavy chain VSMC vascular smooth muscle cell |
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