Affiliation:
1. From the Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children’s Hospital Research Foundation, Children’s Hospital Medical Center, Cincinnati, Ohio, and the Heart Development Group, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta (M.L.K.).
Abstract
Abstract
During fetal development, a specialized vessel, the ductus arteriosus, shunts blood from the pulmonary artery to the aorta, thus bypassing the lungs. The ductus differs primarily from the great vessels in that it is a muscular rather than an elastic artery, and the etiology of this differential development remains controversial. We present evidence that retinoic acid (RA) may contribute to the unique muscle phenotype of the ductus arteriosus. Using a transgenic mouse carrying an RA response element–
lacZ
transgene that expresses β-galactosidase (β-gal) in response to endogenous RA signals during embryonic and fetal development, we observe a strong β-gal signal in the ductus arteriosus. By immunofluorescence, this signal colocalizes with the expression of the adult-specific smooth muscle myosin heavy chain isoform, SM2. The β-gal signal is present throughout fetal development and persists in the neonate until the ductus arteriosus is completely closed. β-Gal–positive cells are first detected by immunofluorescence at 13.5 days postcoitum (dpc) in the mesenchyme surrounding the ductus. By 15.5 dpc, very intense β-gal staining localizes to the ductus arteriosus but is absent or minimal in the pulmonary trunk and aortic arch; by 17.5 dpc, the smooth muscle layers of the tunica media in the ductus arteriosus exhibit positive β-gal staining. Immunostaining with antibodies against smooth muscle myosins shows that, while SM1 is expressed in all embryonic vessels, SM2 is precociously expressed in the ductus arteriosus. Furthermore, SM2 expression can be detected in the ductus as early as 15.5 dpc. In the neonate, the β-gal signal persists in the smooth muscle layer of the ductus and immunostaining colocalizes with SM2 expression. These data suggest that RA may play a role in inducing and maintaining smooth muscle differentiation in the developing ductus arteriosus and may promote precocious expression of the adult vascular phenotype.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Reference56 articles.
1. Control of the ductus arteriosus—A new function for cytochrome P450, Endothelin and nitric oxide
2. Gittenberger-de Groot A. Morphology of the normal human ductus arteriosus. In: Heyman MA Rudolph AM eds. The Ductus Arteriosus: Ross Conferences on Pediatric Research . Columbus Ohio: Ross Laboratories; 1979:3-9.
3. Corbet AJ. Medical manipulation of the ductus arteriosus. In: Garson A Bricker JT McNamara DG eds. The Science and Practice of Pediatric Cardiology . Philadelphia Pa: Lea & Febiger; 1990:2108-2125.
4. Developmentally regulated expression of vascular smooth muscle myosin heavy chain isoforms
Cited by
67 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献