Advertisement

Biomechanics and Modeling in Mechanobiology

, Volume 14, Issue 6, pp 1379–1389 | Cite as

Altered mechanical state in the embryonic heart results in time-dependent decreases in cardiac function

  • Brennan Johnson
  • David BarkJr
  • Ilse Van Herck
  • Deborah Garrity
  • Lakshmi Prasad DasiEmail author
Original Paper

Abstract

Proper blood flow patterns are critical for normal cardiac morphogenesis, a process that occurs rapidly in order to support further development of all tissue and organs. Previously, intracardiac fluid forces have been shown to play a critical role in cardiac morphogenesis. Altered blood flow in early development can result in an array of cardiac defects including ventricular septal defects, valve malformations, and impaired cardiac looping. However, given the dynamic and highly transient nature of cardiac morphogenesis, time dependency of the mechanical environment as an epigenetic factor in relation to intracardiac forces must be significant. Here, we show that abnormal cardiac loading adversely influences cardiac morphology only during certain time windows, thus confirming that mechanical factors are a time-dependent epigenetic factor. To illustrate this, groups of zebrafish embryos were spaced at 6-h increments from 24 to 48 h post-fertilization (hpf) in which embryos were centrifuged to generate a noninvasive alteration of cardiac preload in addition to an overall hypergravity environment. We found that earlier and later treatment groups responded with altered morphology and function, while the group with altered preload from 30 to 36 hpf had no effect. These results demonstrate the inherently time-dependent nature of epigenetic factors as pertaining to intracardiac forces and external mechanical factors. Further, it underscores the highly coupled nature of programmed biology and mechanical forces during cardiac morphogenesis. Future studies with respect to surgical correction during cardiac morphogenesis must consider timing to optimize therapeutic impact.

Keywords

Epigenetics Morphogenesis Mechanobiology Heart tube Peristalsis Pumping Zebrafish Congenital defects 

Notes

Acknowledgments

We acknowledge funding from the National Science Foundation (Award # 1235305).

Supplementary material

Supplementary material 1 (wmv 7177 KB)

Supplementary material 2 (wmv 7083 KB)

References

  1. Antkiewicz DS, Peterson RE, Heideman W (2006) Blocking expression of AHR2 and ARNT1 in zebrafish larvae protects against cardiac toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci 94:175–182CrossRefGoogle Scholar
  2. Bagatto B, Burggren W (2006) A three-dimensional functional assessment of heart and vessel development in the Larva of the Zebrafish (Danio rerio). Physiol Biochem Zool 79:194–201CrossRefGoogle Scholar
  3. Bagatto B, Francl J, Liu B, Liu Q (2006) Cadherin2 (N-cadherin) plays an essential role in zebrafish cardiovascular development. BMC Dev Biol 6:23CrossRefGoogle Scholar
  4. Bakkers J (2011) Zebrafish as a model to study cardiac development and human cardiac disease. Cardiovasc Res 91:279–288. doi: 10.1093/cvr/cvr098 CrossRefGoogle Scholar
  5. Broekhuizen MLA, Hogers B, DeRuiter MC, Poelmann RE, Gittenberger-De Groot AC, Wladimiroff JW (1999) Altered hemodynamics in chick embryos after extraembryonic venous obstruction. Ultrasound Obstet Gynecol 13:437–445. doi: 10.1046/j.1469-0705.1999.13060437.x
  6. Chan J, Mably JD (2011) Dissection of cardiovascular development and disease pathways in zebrafish. In: Chang KT, Min KT (eds) Animal models of human disease, vol 100. Progress in molecular biology and translational science, pp 111–153. doi: 10.1016/b978-0-12-384878-9.00004-2
  7. Driever W et al (1996) A genetic screen for mutations affecting embryogenesis in zebrafish. Development 123:37–46Google Scholar
  8. Gessner IH (1966) Spectrum of congenital cardiac anomalies produced in chick embryos by mechanical interference with cardiogenesis. Circ Res 18:625–633. doi: 10.1161/01.res.18.6.625 CrossRefGoogle Scholar
  9. Groenendijk BCW, Van der Heiden K, Hierck BP, Poelmann RE (2007) The role of shear stress on ET-1, KLF2, and NOS-3 expression in the developing cardiovascular system of chicken embryos in a venous Ligation model. Physiology 22:380–389. doi: 10.1152/physiol.00023.2007 CrossRefGoogle Scholar
  10. Hogers B, DeRuiter MC, Gittenberger-de Groot AC, Poelmann RE (1999) Extraembryonic venous obstructions lead to cardiovascular malformations and can be embryolethal. Cardiovasc Res 41:87–99Google Scholar
  11. Hogers B, DeRuiter MC, GittenbergerdeGroot AC, Poelmam RE (1997) Unilateral vitelline vein ligation alters intracardiac blood flow patterns and morphogenesis in the chick embryo. Circul Res 80:473–481CrossRefGoogle Scholar
  12. Hove JR, Koster RW, Forouhar AS, Acevedo-Bolton G, Fraser SE, Gharib M (2003) Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421:172–177. doi: 10.1038/nature01282 CrossRefGoogle Scholar
  13. Hu N, Yost HJ, Clark EB (2001) Cardiac morphology and blood pressure in the adult zebrafish. Anat Rec 264:1–12. doi: 10.1002/ar.1111 CrossRefGoogle Scholar
  14. Johnson BM, Garrity DM, Dasi LP (2013a) Quantifying function in the early embryonic heart. J Biomech Eng Trans Asme 135. doi: 10.1115/1.4023701
  15. Johnson BM, Garrity DM, Dasi LP (2013b) The transitional cardiac pumping mechanics in the embryonic heart cardiovascular engineering and technologyGoogle Scholar
  16. Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203:253–310CrossRefGoogle Scholar
  17. Liebling M et al (2006) Rapid three-dimensional imaging and analysis of the beating embryonic heart reveals functional changes during development. Dev Dyn 235:2940–2948. doi: 10.1002/dvdy.20926 CrossRefGoogle Scholar
  18. Malone MH, Sciaky N, Stalheim L, Hahn KM, Linney E, Johnson GL (2007) Laser-scanning velocimetry: a confocal microscopy method for quantitative measurement of cardiovascular performance in zebrafish embryos and larvae. BMC Biotechnol 7:40CrossRefGoogle Scholar
  19. Manner J, Wessel A, Yelbuz TM (2010) How does the tubular embryonic heart work? Looking for the physical mechanism generating unidirectional blood flow in the valveless embryonic heart tube. Dev Dyn 239:1035–1046. doi: 10.1002/dvdy.22265 CrossRefGoogle Scholar
  20. Parrie LE, Renfrew EM, Vander Wal A, Mueller RL, Garrity DM (2013) Zebrafish tbx5 paralogs demonstrate independent essential requirements in cardiac and pectoral fin development. Dev Dyn 242:485–502. doi: 10.1002/dvdy.23953 CrossRefGoogle Scholar
  21. Poon KL, Liebling M, Kondrychyn I, Garcia-Lecea M, Korzh V (2010) Zebrafish cardiac enhancer trap lines: new tools for in vivo studies of cardiovascular development and disease. Dev Dyn 239:914–926. doi: 10.1002/dvdy.22203 CrossRefGoogle Scholar
  22. Reckova M et al (2003) Hemodynamics is a key epigenetic factor in development of the cardiac conduction system. Circ Res 93:77–85. doi: 10.1161/01.res.0000079488.91342.b7
  23. Santhanakrishnan A, Miller LA (2011) Fluid dynamics of heart development. Cell Biochem Biophys 61:1–22. doi: 10.1007/s12013-011-9158-8 CrossRefGoogle Scholar
  24. Shi Y, Yao J, Young JM, Fee JA, Perucchio R, Taber LA (2014) Bending and twisting the embryonic heart: a computational model for C-looping based on realistic geometry. Front Physiol 5. doi: 10.3389/fphys.2014.00297
  25. Sluysmans T, Colan SD (2005) Theoretical and empirical derivation of cardiovascular allometric relationships in children. J Appl Physiol 99:445–457. doi: 10.1152/japplphysiol.01144.2004 CrossRefGoogle Scholar
  26. Stainier DYR, Lee RK, Fishman MC (1993) Cardiovascular development in the zebrafish 1. Myocardial fate map and heart tube formation. Development 119:31–40Google Scholar
  27. Thisse C, Zon LI (2002) Development—organogenesis—heart and wood formation from the zebrafish point of view. Science 295:457–462. doi: 10.1126/science.1063654 CrossRefGoogle Scholar
  28. Tobita K, Garrison JB, Liu LJ, Tinney JP, Keller BB (2005) Three-dimensional myofiber architecture of the embryonic left ventricle during normal development and altered mechanical loads. Anat Rec Part A Discov Mol Cell Evol Biol 283A:193–201. doi: 10.1002/ar.a.20133
  29. Traver D, Paw BH, Poss KD, Penberthy WT, Lin S, Zon LI (2003) Transplantation and in vivo imaging of multilineage engraftment in zebrafish bloodless mutants. Nat Immunol 4(12):1238–1246CrossRefGoogle Scholar
  30. Westerfield M (1995) The zebrafish book. University of Oregon Press, EugeneGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Brennan Johnson
    • 1
  • David BarkJr
    • 1
  • Ilse Van Herck
    • 2
  • Deborah Garrity
    • 2
  • Lakshmi Prasad Dasi
    • 1
    Email author
  1. 1.Department of Mechanical EngineeringColorado State UniversityFort CollinsUSA
  2. 2.Department of BiologyColorado State UniversityFort CollinsUSA

Personalised recommendations