Circulation Research, Vol 74, 244-252, Copyright © 1994 by American Heart Association

ARTICLES

Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ

HS Baldwin, TR Lloyd and M Solursh
Department of Pediatrics (Cardiology), University of Pennsylvania/Children's Hospital of Philadelphia 19014.

Hyaluronic acid is the major glycosaminoglycan of the early cardiac extracellular matrix or "cardiac jelly," yet little is known about its role in the ontogeny of early ventricular performance. To investigate the in situ effect of hyaluronate degradation on ventricular function, whole rat embryos were cultured in rat serum alone (control embryos) or rat serum plus 20 TRU/mL of Streptomyces hyaluronidase (treatment embryos) from gestational day 9.5 (before formation of the heart tube) through initial looping of the heart. Cardiac function was measured before looping (24 hours in culture) and immediately after looping (36 hours in culture) by video motion analysis of the external wall motion of the bulbus cordis and primitive ventricle. Degradation of hyaluronic acid in the treated embryos was confirmed by Alcian blue staining at pH 2.5. Significant increases in heart rate, circumferential shortening fraction, maximum velocity of circumferential contraction, and maximum velocity of circumferential relaxation were observed with looping in both control and treatment embryos. Although there was minimal difference in ventricular performance between control and treatment embryos before looping, there was a significant increase in all parameters of ventricular performance in the hyaluronidase-treated embryos immediately after looping of the heart. Endocardial cushions were absent in hyaluronidase-treated embryos, and an additional group of embryos cultured in the presence of Streptomyces hyaluronidase for 48 to 72 hours failed to develop endocardial cushions. These experiments are the first to (1) document a quantifiable increase in ventricular performance during early cardiac looping and (2) demonstrate that hyaluronate degradation results in abnormal endocardial cushion formation and altered ventricular performance of the postlooped heart.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				M. Shirai, K. Imanaka-Yoshida, M. D. Schneider, R. J. Schwartz, and T. Morisaki T-box 2, a mediator of Bmp-Smad signaling, induced hyaluronan synthase 2 and Tgf{beta}2 expression and endocardial cushion formation PNAS, November 3, 2009; 106(44): 18604 - 18609. [Abstract] [Full Text] [PDF]

				J. T Butcher and R. R Markwald Valvulogenesis: the moving target Phil Trans R Soc B, August 29, 2007; 362(1484): 1489 - 1503. [Abstract] [Full Text] [PDF]

				L. S. Rodgers, S. Lalani, K. M. Hardy, X. Xiang, D. Broka, P. B. Antin, and T. D. Camenisch Depolymerized Hyaluronan Induces Vascular Endothelial Growth Factor, a Negative Regulator of Developmental Epithelial-to-Mesenchymal Transformation Circ. Res., September 15, 2006; 99(6): 583 - 589. [Abstract] [Full Text] [PDF]

				J.-M. Gu, J. T. B. Crawley, G. Ferrell, F. Zhang, W. Li, N. L. Esmon, and C. T. Esmon Disruption of the Endothelial Cell Protein C Receptor Gene in Mice Causes Placental Thrombosis and Early Embryonic Lethality J. Biol. Chem., November 1, 2002; 277(45): 43335 - 43343. [Abstract] [Full Text] [PDF]

				S. Srinivasan, H. S. Baldwin, O. Aristizabal, L. Kwee, M. Labow, M. Artman, and D. H. Turnbull Noninvasive, In Utero Imaging of Mouse Embryonic Heart Development With 40-MHz Echocardiography Circulation, September 1, 1998; 98(9): 912 - 918. [Abstract] [Full Text] [PDF]

				P Gakunga, G Frost, S Shuster, G Cunha, B Formby, and R Stern Hyaluronan is a prerequisite for ductal branching morphogenesis Development, January 10, 1997; 124(20): 3987 - 3997. [Abstract] [PDF]

				A. P. Spicer, M. L. Augustine, and J. A. McDonald Molecular Cloning and Characterization of a Putative Mouse Hyaluronan Synthase J. Biol. Chem., September 20, 1996; 271(38): 23400 - 23406. [Abstract] [Full Text] [PDF]