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Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis

Hove, Jay R. and Köster, Reinhard W. and Forouhar, Arian S. and Acevedo-Bolton, Gabriel and Fraser, Scott E. and Gharib, Morteza (2003) Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature, 421 (6919). pp. 172-177. ISSN 0028-0836. doi:10.1038/nature01282.

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The pattern of blood flow in the developing heart has long been proposed to play a significant role in cardiac morphogenesis. In response to flow-induced forces, cultured cardiac endothelial cells rearrange their cytoskeletal structure and change their gene expression profiles. To link such in vitro data to the intact heart, we performed quantitative in vivo analyses of intracardiac flow forces in zebrafish embryos. Using in vivo imaging, here we show the presence of high-shear, vortical flow at two key stages in the developing heart, and predict flow-induced forces much greater than might have been expected for micro-scale structures at low Reynolds numbers. To test the relevance of these shear forces in vivo, flow was occluded at either the cardiac inflow or outflow tracts, resulting in hearts with an abnormal third chamber, diminished looping and impaired valve formation. The similarity of these defects to those observed in some congenital heart diseases argues for the importance of intracardiac haemodynamics as a key epigenetic factor in embryonic cardiogenesis.

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Fraser, Scott E.0000-0002-5377-0223
Gharib, Morteza0000-0002-2204-9302
Additional Information:© 2003 Nature Publishing Group. Received 9 August 2002; Accepted 31 October 2002. We thank S. Lin for the stable transgenic gata1::GFP zebrafish strain, E. Walsh, E. Ober, B. Jungblut and D.Y.R. Stainier for the transgenic tie2::GFP strain and comments on the manuscript and M. Bak and Y. Gong for discussions. This work was supported by the American Heart Association (J.R.H.) and the Human Frontier Science Program (R.W.K.), the NIH (S.E.F.), the Beckman Institute at Caltech and the Powell Foundation. J.R.H. worked on flow pattern analysis and calculations. R.W.K. worked on imaging and embryonic manipulation. Competing interests statement: The authors declare that they have no competing financial interests.
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American Heart AssociationUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Powell FoundationUNSPECIFIED
Issue or Number:6919
Record Number:CaltechAUTHORS:20130911-103554285
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:41245
Deposited By: Tony Diaz
Deposited On:11 Sep 2013 22:26
Last Modified:10 Nov 2021 04:27

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