TY - JOUR
T1 - Premature differentiation of vascular smooth muscle cells in human congenital diaphragmatic hernia
AU - Sluiter, Ilona
AU - van der Horst, Irene
AU - van der Voorn, Paul
AU - Boerema-de Munck, Anne
AU - Buscop-van Kempen, Marjon
AU - de Krijger, Ronald
AU - Tibboel, Dick
AU - Reiss, Irwin
AU - Rottier, Robbert J.
N1 - Funding Information:
Ilona Sluiter is supported in part by the Sophia Foundation for Medical Research project SSWO number 521 .
PY - 2013/2
Y1 - 2013/2
N2 - Background: Congenital 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. Methodology: We 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. Results: Synthetic 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. Conclusion: Our 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.
AB - Background: Congenital 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. Methodology: We 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. Results: Synthetic 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. Conclusion: Our 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.
KW - Congenital diaphragmatic hernia
KW - Pulmonary vascular development
KW - Smooth muscle cells
UR - http://www.scopus.com/inward/record.url?scp=84870921430&partnerID=8YFLogxK
U2 - 10.1016/j.yexmp.2012.09.010
DO - 10.1016/j.yexmp.2012.09.010
M3 - Article
C2 - 23018129
AN - SCOPUS:84870921430
SN - 0014-4800
VL - 94
SP - 195
EP - 202
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 1
ER -