title: Effects of platelet-derived growth factor-AA and -BB on embryonic cardiac development.
abstract: Several studies have shown that disruption of the normal expression patterns of platelet-derived growth factor (PDGF) ligands and receptors during development results in gross cardiac defects and embryonic or neonatal death. However, little is known about the specific role that PDGF plays in the differentiation of cardiac myocytes. In experiments complementing studies that utilized naturally-occurring Patch mice lacking the PDGFr alpha, or knockout animals lacking a PDGF ligand or receptor, we used rat and mouse whole-embryo culture (WEC) techniques to increase the exposure of embryos to the PDGF-AA or -BB ligands. Following a 48-hr culture period, we analyzed heart growth and cardiac myocyte differentiation. Exposure of rat embryos to 50 ng/ml of PDGF-AA resulted in a 42% increase in total protein levels in the heart, but did not result in a significant increase in heart growth, as determined by measurements of the atrioventricular length and the left ventricular length and width. Exposure of embryos to 50 ng/ml of PDGF-BB resulted in a 77% increase in total protein levels and a significant (P < 0.05) 8-15% increase in the measured heart parameters. Although a comparison of control and PDGF-AA-treated embryos showed no increase in the overall size of the heart, confocal microscopy showed an increase in the size and number of myofibrillar bundles in the developing myocardium. In addition, transmission electron microscopy (TEM) revealed an increase in the presence of sarcomeres, indicating that myofibrils were more highly differentiated in these areas of the treated embryos. In PDGF-BB-treated embryos, the compact zone of the myocardium was thicker and, as shown by confocal microscopy and TEM, f-actin and well-developed sarcomeres were more prevalent, indicating that the myofibrils were more differentiated in the treated embryos than in the control embryos. These studies indicate that increased exposure of embryonic hearts to PDGF-AA or -BB increases the rate of myocardial development.
authors.affiliation: Department of Developmental Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Price
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Haley
authors.forename: Tara A
authors.initials: TA
authors.lastname: Bullard
authors.forename: Edie C
authors.initials: EC
authors.lastname: Goldsmith
authors.forename: David G
authors.initials: DG
authors.lastname: Simpson
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Thielen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yost
authors.forename: Louis
authors.initials: L
authors.lastname: Terracio
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta