© 1996 American Heart Association, Inc.
Articles |
Endogenous Retinoic Acid Signaling Colocalizes With Advanced Expression of the Adult Smooth Muscle Myosin Heavy Chain Isoform During Development of the Ductus Arteriosus
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.).
Correspondence to Jeffrey Robbins, Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children's Hospital Research Foundation, Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229. E-mail teachdna@aol.com.
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 ß-galactosidase (ß-gal) in response to endogenous RA signals during embryonic and fetal development, we observe a strong ß-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 ß-gal signal is present throughout fetal development and persists in the neonate until the ductus arteriosus is completely closed. ß-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 ß-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 ß-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 ß-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.
Key Words: retinoic acid • ductus arteriosus • smooth muscle myosin heavy chain • mouse • development
This article has been cited by other articles:
 |
|
 |
|
  U. Yokoyama, Y. Sato, T. Akaike, S. Ishida, J. Sawada, T. Nagao, H. Quan, M. Jin, M. Iwamoto, S. Yokota, et al. Maternal vitamin A alters gene profiles and structural maturation of the rat ductus arteriosus Physiol Genomics, September 11, 2007; 31(1): 139 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kota, M. Osborne-Pellegrin, H. Schulz, J. Behmoaras, M. Coutard, M. Gong, and N. Hubner Quantitative genetic basis of arterial phenotypes in the Brown Norway rat Physiol Genomics, June 19, 2007; 30(1): 17 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Agren, A. L. Cogolludo, C. G. A. Kessels, F. Perez-Vizcaino, J. G. R. De Mey, C. E. Blanco, and E. Villamor Ontogeny of chicken ductus arteriosus response to oxygen and vasoconstrictors Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R485 - R496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nakamura, M. C. Colbert, and J. Robbins Neural Crest Cells Retain Multipotential Characteristics in the Developing Valves and Label the Cardiac Conduction System Circ. Res., June 23, 2006; 98(12): 1547 - 1554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Yokoyama, S. Minamisawa, S. Adachi-Akahane, T. Akaike, I. Naguro, K. Funakoshi, M. Iwamoto, M. Nakagome, N. Uemura, H. Hori, et al. Multiple transcripts of Ca2+ channel {alpha}1-subunits and a novel spliced variant of the {alpha}1C-subunit in rat ductus arteriosus Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1660 - H1670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. R. Paiva, L. S. Matsubara, B. B. Matsubara, M. F. Minicucci, P. S. Azevedo, A. O. Campana, and L. A. M. Zornoff Retinoic Acid Supplementation Attenuates Ventricular Remodeling after Myocardial Infarction in Rats J. Nutr., October 1, 2005; 135(10): 2326 - 2328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Thebaud, E. D. Michelakis, X.-C. Wu, R. Moudgil, M. Kuzyk, J. R.B. Dyck, G. Harry, K. Hashimoto, A. Haromy, I. Rebeyka, et al. Oxygen-Sensitive Kv Channel Gene Transfer Confers Oxygen Responsiveness to Preterm Rabbit and Remodeled Human Ductus Arteriosus: Implications for Infants With Patent Ductus Arteriosus Circulation, September 14, 2004; 110(11): 1372 - 1379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. R. de Paiva, L. A. M. Zornoff, M. P. Okoshi, K. Okoshi, L. S. Matsubara, B. B. Matsubara, A. C. Cicogna, and A. O. Campana Ventricular remodeling induced by retinoic acid supplementation in adult rats Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2242 - H2246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Miano and B. C. Berk Retinoids : Versatile Biological Response Modifiers of Vascular Smooth Muscle Phenotype Circ. Res., September 1, 2000; 87(5): 355 - 362. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Neuville, M.-L. Bochaton-Piallat, and G. Gabbiani Retinoids and Arterial Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., August 1, 2000; 20(8): 1882 - 1888. [Full Text] [PDF]
|
|
|
|
 |
|
 S.-i. Imamura, T. Nishikawa, E. Hiratsuka, A. Takao, and R. Matsuoka Behavior of Smooth Muscle Cells during Arterial Ductal Closure at Birth J. Histochem. Cytochem., January 1, 2000; 48(1): 35 - 44. [Abstract] [Full Text]
|
|
|
|
|
|
Q. Yang, A. Sanbe, H. Osinska, T. E. Hewett, R. Klevitsky, and J. Robbins In Vivo Modeling of Myosin Binding Protein C Familial Hypertrophic Cardiomyopathy Circ. Res., October 29, 1999; 85(9): 841 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bergwerff, M. C. DeRuiter, S. Hall, R. E. Poelmann, and A. C. Gittenberger-de Groot Unique vascular morphology of the fourth aortic arches: possible implications for pathogenesis of type-B aortic arch interruption and anomalous right subclavian artery Cardiovasc Res, October 1, 1999; 44(1): 185 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Christen, M.-L. Bochaton-Piallat, P. Neuville, S. Rensen, M. Redard, G. van Eys, and G. Gabbiani Cultured Porcine Coronary Artery Smooth Muscle Cells : A New Model With Advanced Differentiation Circ. Res., July 9, 1999; 85(1): 99 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Neuville, Z.-q Yan, A. Gidlof, M. S. Pepper, G. K. Hansson, G. Gabbiani, and A. Sirsjo Retinoic Acid Regulates Arterial Smooth Muscle Cell Proliferation and Phenotypic Features In Vivo and In Vitro Through an RAR{alpha}-Dependent Signaling Pathway Arterioscler. Thromb. Vasc. Biol., June 1, 1999; 19(6): 1430 - 1436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Arens, R. A. Chapados, B. E. Cox, K. E. Kamm, and C. R. Rosenfeld Differential development of umbilical and systemic arteries. II. Contractile proteins Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1998; 274(6): R1815 - R1823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. S. Smith The Pharmacology of the Ductus Arteriosus Pharmacol. Rev., March 1, 1998; 50(1): 35 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Searcy, E. Vincent, C. Liberatore, and K. Yutzey A GATA-dependent nkx-2.5 regulatory element activates early cardiac gene expression in transgenic mice Development, January 11, 1998; 125(22): 4461 - 4470. [Abstract] [PDF]
|
|
|
|
|
|
S. Sartore, A. Chiavegato, R. Franch, E. Faggin, and P. Pauletto Myosin Gene Expression and Cell Phenotypes in Vascular Smooth Muscle During Development, in Experimental Models, and in Vascular Disease Arterioscler. Thromb. Vasc. Biol., July 1, 1997; 17(7): 1210 - 1215. [Abstract] [Full Text]
|
|
|
|
|
|
J. Gulick, T. E. Hewett, R. Klevitsky, S. H. Buck, R. L. Moss, and J. Robbins Transgenic Remodeling of the Regulatory Myosin Light Chains in the Mammalian Heart Circ. Res., May 19, 1997; 80(5): 655 - 664. [Abstract] [Full Text]
|
|