The Endothelin-1 Pathway and the Development of Cardiovascular Defects in the Haemodynamically Challenged Chicken EmbryoGroenendijk B.C.W.a, d · Stekelenburg-de Vos S.b · Vennemann P.c · Wladimiroff J.W.b · Nieuwstadt F.T.M.c · Lindken R.c · Westerweel J.c · Hierck B.P.a · Ursem N.T.C.b · Poelmann R.E.a
aDepartment of Anatomy and Embryology, Leiden University Medical Center, Leiden, bDepartment of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, cDepartment of Aero- and Hydrodynamics, Delft University of Technology, Delft, and dDepartment of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands
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Article / Publication Details
Background/Aims: Ligating the right lateral vitelline vein of chicken embryos (venous clip) results in cardiovascular malformations. These abnormalities are similar to malformations observed in knockout mice studies of components of the endothelin-1 (ET-1)/endothelin-converting enzyme-1/endothelin-A receptor pathway. In previous studies we demonstrated that cardiac ET-1 expression is decreased 3 h after clipping, and ventricular diastolic filling is disturbed after 2 days. Therefore, we hypothesise that ET-1-related processes are involved in the development of functional and morphological cardiovascular defects after venous clip. Methods: In this study, ET-1 and endothelin receptor antagonists (BQ-123, BQ-788 and PD145065) were infused into the HH18 embryonic circulation. Immediate haemodynamic effects on the embryonic heart and extra-embryonic vitelline veins were examined by Doppler and micro-particle image velocimetry. Ventricular diastolic filling characteristics were studied at HH24, followed by cardiovascular morphologic investigation (HH35). Results: ET-1 and its receptor antagonists induced haemodynamic effects at HH18. At HH24, a reduced diastolic ventricular passive filling component was demonstrated, which was compensated by an increased active filling component. Thinner ventricular myocardium was shown in 42% of experimental embryos. Conclusion: We conclude that cardiovascular malformations after venous clipping arise from a combination of haemodynamic changes and altered gene expression patterns and levels, including those of the endothelin pathway.
© 2007 S. Karger AG, Basel
- Hove JR, Koster RW, Forouhar AS, Acevedo-Bolton G, Fraser SE, Gharib M: Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 2003;421:172–177.
- Hogers B, DeRuiter MC, Gittenberger-de Groot AC, Poelmann RE: Extraembryonic venous obstructions lead to cardiovascular malformations and can be embryolethal. Cardiovasc Res 1999;41:87–99.
- McCormick SM, Eskin SG, McIntire LV, Teng CL, Lu CM, Russell CG, Chittur KK: DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells. Proc Natl Acad Sci USA 2001;98:8955–8960.
- Dekker RJ, Van Soest S, Fontijn RD, Salamanca S, de Groot PG, VanBavel E, Pannekoek H, Horrevoets AJG: Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Krüppel-like factor (KLF2). Blood 2002;100:1689–1698.
- Groenendijk BCW, Hierck BP, Gittenberger-de Groot AC, Poelmann RE: Development-related changes in the expression of shear stress responsive genes KLF-2, ET-1, and NOS-3 in the developing cardiovascular system of chicken embryos. Dev Dyn 2004;230:57–68.
- Hamburger V, Hamilton HL: A series of normal stages in the development of the chick embryo. J Morphol 1951;88:49–92.
- Hogers B, DeRuiter MC, Gittenberger-de Groot AC, Poelmann RE: Unilateral vitelline vein ligation alters intracardiac blood flow patterns and morphogenesis in the chick embryo. Circ Res 1997;80:473–481.
- Stekelenburg-de Vos S, Ursem NTC, Hop WCJ, Wladimiroff JW, Gittenberger-de Groot AC, Poelmann RE: Acutely altered hemodynamics following venous obstruction in the early chick embryo. J Exp Biol 2003;206:1051–1057.
- Groenendijk BCW, Hierck BP, Vrolijk J, Baiker M, Pourquie MJBM, Gittenberger-de Groot AC, Poelmann RE: Changes in shear stress-related gene expression after experimentally altered venous return in the chicken embryo. Circ Res 2005;96:1291–1298.
- Stekelenburg-de Vos S, Steendijk P, Ursem NT, Wladimiroff JW, Delfos R, Poelmann RE: Systolic and diastolic ventricular function assessed by pressure-volume loops in the stage 21 venous clipped chick embryo. Pediatr Res 2005;57:16–21.
- Ursem NTC, Stekelenburg-de Vos S, Wladimiroff JW, Poelmann RE, Gittenberger-de Groot AC, Hu N, Clark EB: Ventricular diastolic filling characteristics in stage-24 chick embryos after extra-embryonic venous obstruction. J Exp Biol 2004;207:1487–1490.
- Kurihara Y, Kurihara H, Oda H, Maemura K, Nagai R, Ishikawa T, Yazaki Y: Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1. J Clin Invest 1995;96:293–300.
- Yanagisawa H, Yanagisawa M, Kapur RP, Richardson JA, Williams SC, Clouthier DE, de Wit D, Emoto N, Hammer RE: Dual genetic pathways of endothelin-mediated intercellular signaling revealed by targeted disruption of endothelin converting enzyme-1 gene. Development 1998;125:825–836.
- Clouthier DE, Hosoda K, Richardson JA, Williams SC, Yanagisawa H, Kuwaki T, Kumada M, Hammer RE, Yanagisawa M: Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice. Development 1998;125:813–824.
- Ursem NTC, Struijk PC, Poelmann RE, Gittenberger-de Groot AC, Wladimiroff JW: Dorsal aortic flow velocity in chick embryos of stage 16 to 28. Ultrasound Med Biol 2001;27:919–924.
- Nakazawa M, Clark EB, Hu N, Wispe J: Effect of environmental hypothermia in vitelline artery blood pressure and vascular resistance in the stage 18, 21, and 24 chick embryo. Pediatr Res 1985;19:651–654.
- Hu N, Connuck DM, Keller BB, Clark EB: Diastolic filling characteristics in the stage 12 to 27 chick embryo ventricle. Pediatr Res 1991;29:334–337.
- Vennemann P, Kiger KT, Lindken R, Groenendijk BCW, Stekelenburg-de Vos S, ten Hagen TLM, Ursem NTC, Poelmann RE, Westerweel J, Hierck BP: In vivo micro particle image velocimetry measurements of blood-plasma in the embryonic avian heart. J Biomech 2006;39:1191–1200.
- Meinhart C, Wereley S, Santiago J: A PIV algorithm for estimating time-averaged velocity fields. J Fluids Eng 2000;122:285–289.
- Tsukada T, Tippens D, Gordon D, Ross R, Gown AM: HHF35, a muscle-actin-specific monoclonal antibody. I. Immunocytochemical and biochemical characterization. Am J Pathol 1987;126:51–60.
- Hierck BP, Poelmann RE, van Iperen L, Brouwer A, Gittenberger-de Groot AC: Differential expression of α6 and other subunits of laminin binding integrins during development of the murine heart. Dev Dyn 1996;206:100–111.
- Hierck BP, Molin DGM, Boot MJ, Poelmann RE, Gittenberger-de Groot AC: A chicken model for DGCR6 as a modifier gene in the DiGeorge critical region. Pediatr Res 2004;56:440–448.
- Rozen S, Skaletsky H: Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000;132:365–386.
Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001;29:2002–2007.
- Broekhuizen MLA, Mast F, Struijk, van der Bie W, Mulder PGH, Gittenberger-de Groot AC, Wladimiroff J: Hemodynamic parameters of stage 20 to stage 35 chick embryo. Pediatr Res 1993;34:44–46.
- Hu N, Clark EB: Hemodynamics of the stage 12 to stage 29 chick embryo. Circ Res 1989;65:1665–1670.
- Yoshigi M, Hu N, Keller BB: Dorsal aortic impedance in stage 24 chick embryo following acute changes in circulating blood volume. Am J Physiol 1996;270:H1597–H1606.
- Vrancken Peeters M-PFM, Mentink MMT, Poelmann RE, Gittenberger-de Groot AC: Cytokeratins as a marker for epicardial formation in the quail embryo. Anat Embryol 1995;191:503–508.
- Hosoda K, Nakao K, Hiroshi A, Suga S, Ogawa Y, Mukoyama M, Shirakami G, Saito Y, Nakanishi S, Imura H: Cloning and expression of human endothelin-1 receptor cDNA. FEBS Lett 1991;287:23–26.
- Haynes WG, Strachan FE, Webb DJ: Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation 1995;92:357–363.
- Tsukahara H, Ende H, Magazine HI, Bahou WF, Goligorsky MS: Molecular and functional characterization of the non-isopeptide-selective ETB receptor in endothelial cells: receptor coupling to nitric oxide synthase. J Biol Chem 1994;269:21778–21785.
- Verhaar MC, Strachan FE, Newby DE, Cruden NL, Koomans HA, Rabelink TJ, Webb DJ: Endothelin-A receptor antagonist-mediated vasodilatation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B receptor blockade. Circulation 1998;97:752–756.
- Berthiaume N, Yanagisawa M, Labonte J, D’Orleans-Juste P: Heterozygous knock-out of ET(B) receptors induces BQ-123-sensitive hypertension in the mouse. Hypertension 2000;36:1002–1007.
- D’Orleans-Juste P, Labonte J, Bkaily G, Choufani S, Plante M, Honore JC: Function of the endothelin(B) receptor in cardiovascular physiology and pathophysiology. Pharmacol Ther 2002;95:221–238.
- Hirata Y, Emori T, Eguchi S, Kanno K, Imai T, Ohta K, Marumo F: Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J Clin Invest 1993;91:1367–1373.
- Leite-Moreira AF, Bras-Silva C, Pedrosa CA, Rocha-Sousa AA: ET-1 increases distensibility of acutely loaded myocardium: a novel ETA and Na+/H+ exchanger-mediated effect. Am J Physiol Heart Circ Physiol 2003;284:H1332–H1339.
- Marsault R, Feolde E, Frelin C: Receptor externalization determines sustained contractile responses to endothelin-1 in the rat aorta. Am J Physiol 1993;264:C687–C693.
- Kajio F, Nakazawa M: Vascular effects of endothelin-1 in stage 21 chick embryos. Heart Vessels 1997;12:300–305.
- Kelso EJ, McDermott BJ, Silke B, Spiers JP: EndothelinA receptor subtype mediates endothelin-induced contractility in left ventricular cardiomyocytes isolated from rabbit myocardium. J Pharmacol Exp Ther 2000;294:1047–1052.
- Vierhapper H, Wagner O, Nowotny P, Waldhausl W: Effect of endothelin-1 in man. Circulation 1990;81:1415–1418.
- Sirviö ML, Metsärinne K, Saijonmaa O, Fyhrquist F: Tissue distribution and half-life of I-125 endothelin in the rat – importance of pulmonary clearance. Biochem Biophys Res Commun 1990;167:1191–1195.
- Guarda E, Katwa LC, Myers PR, Tyagi SC, Weber KT: Effects of endothelins on collagen turnover in cardiac fibroblasts. Cardiovasc Res 1993;27:2130–2134.
- Fujisaki H, Ito H, Hirata Y, Tanaka M, Hata M, Lin MH, Adachi S, Akimoto H, Marumo F, Hiroe M: Natriuretic peptides inhibit angiotensin II-induced proliferation of rat cardiac fibroblasts by blocking endothelin-1 gene-expression. J Clin Invest 1995;96:1059–1065.
Hogers B, Gittenberger-de Groot AC, DeRuiter MC, Mentink MMT, Poelmann RE: Cardiac inflow malformations are more lethal and precede cardiac outflow malformations: chick embryonic venous clip model; in Hogers B (ed): The Role of Blood Flow in Normal and Abnormal Heart Development. Wageningen, Ponsen & Looijen BV, 1998, pp 79–100.
- Lie-Venema H, Gittenberger-de Groot AC, van Empel LJP, Boot MJ, Kerkdijk H, de Kant E, DeRuiter MC: Ets-1 and Ets-2 transcription factors are essential for normal coronary and myocardial development in chicken embryos. Circ Res 2003;92:749–756.
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