title: Critical transitions in early embryonic aortic arch patterning and hemodynamics.
abstract: Transformation from the bilaterally symmetric embryonic aortic arches to the mature great vessels is a complex morphogenetic process, requiring both vasculogenic and angiogenic mechanisms. Early aortic arch development occurs simultaneously with rapid changes in pulsatile blood flow, ventricular function, and downstream impedance in both invertebrate and vertebrate species. These dynamic biomechanical environmental landscapes provide critical epigenetic cues for vascular growth and remodeling. In our previous work, we examined hemodynamic loading and aortic arch growth in the chick embryo at Hamburger-Hamilton stages 18 and 24. We provided the first quantitative correlation between wall shear stress (WSS) and aortic arch diameter in the developing embryo, and observed that these two stages contained different aortic arch patterns with no inter-embryo variation. In the present study, we investigate these biomechanical events in the intermediate stage 21 to determine insights into this critical transition. We performed fluorescent dye microinjections to identify aortic arch patterns and measured diameters using both injection recordings and high-resolution optical coherence tomography. Flow and WSS were quantified with 3D computational fluid dynamics (CFD). Dye injections revealed that the transition in aortic arch pattern is not a uniform process and multiple configurations were documented at stage 21. CFD analysis showed that WSS is substantially elevated compared to both the previous (stage 18) and subsequent (stage 24) developmental time-points. These results demonstrate that acute increases in WSS are followed by a period of vascular remodeling to restore normative hemodynamic loading. Fluctuations in blood flow are one possible mechanism that impacts the timing of events such as aortic arch regression and generation, leading to the variable configurations at stage 21. Aortic arch variations noted during normal rapid vascular remodeling at stage 21 identify a temporal window of increased vulnerability to aberrant aortic arch morphogenesis with the potential for profound effects on subsequent cardiovascular morphogenesis.
authors.affiliation: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Kowalski
authors.forename: Onur
authors.initials: O
authors.lastname: Dur
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Patrick
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Tinney
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Keller
authors.forename: Kerem
authors.initials: K
authors.lastname: Pekkan
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology* / Q000502:physiology*; D002642:Chick Embryo; D006439:Hemodynamics / Q000502:physiology*
references.citation: Am J Physiol. 1996 Jan;270(1 Pt 2):H364-75
references.pmid: 8769773
references.citation: J Morphol. 1951 Jan;88(1):49-92
references.pmid: 24539719
references.citation: Nature. 2003 Jan 9;421(6919):172-7
references.pmid: 12520305
references.citation: Circ Res. 1989 Dec;65(6):1665-70
references.pmid: 2582595
references.citation: Dev Biol. 2005 May 1;281(1):78-90
references.pmid: 15848390
references.citation: Comput Methods Programs Biomed. 2000 Aug;63(1):29-41
references.pmid: 10927152
references.citation: Bull Math Biol. 1984;46(1):127-37
references.pmid: 6713148
references.citation: Dev Dyn. 2005 Aug;233(4):1217-37
references.pmid: 15986452
references.citation: Circ Res. 2003 Jul 11;93(1):77-85
references.pmid: 12775585
references.citation: Circ Res. 1966 Jun;18(6):625-33
references.pmid: 5935205
references.citation: Microcirculation. 2010 Apr;17(3):164-78
references.pmid: 20374481
references.citation: Am J Physiol. 1980 Jul;239(1):H14-21
references.pmid: 7396013
references.citation: Ultrasound Med Biol. 2001 Jul;27(7):919-24
references.pmid: 11476925
references.citation: Lancet. 1986 Feb 8;1(8476):307-10
references.pmid: 2868172
references.citation: Anat Rec. 1999 Feb 1;254(2):238-52
references.pmid: 9972809
references.citation: Circulation. 2002 Nov 26;106(22):2771-4
references.pmid: 12451001
references.citation: Cardiovasc Res. 1973 Sep;7(5):670-5
references.pmid: 4753301
references.citation: Anat Rec (Hoboken). 2009 May;292(5):652-60
references.pmid: 19322826
references.citation: Anat Rec A Discov Mol Cell Evol Biol. 2005 Mar;283(1):193-201
references.pmid: 15678488
references.citation: Circ Res. 1982 Dec;51(6):810-5
references.pmid: 7139890
references.citation: Adv Exp Med Biol. 1992;316:31-9
references.pmid: 1288092
references.citation: Circ Res. 2007 May 11;100(9):1363-70
references.pmid: 17413043
references.citation: Biomech Model Mechanobiol. 2012 Sep;11(7):1057-73
references.pmid: 22307681
references.citation: Circ Res. 1986 Nov;59(5):545-50
references.pmid: 3802428
references.citation: Development. 2011 Apr;138(8):1573-82
references.pmid: 21389051
references.citation: J Invest Dermatol. 1981 Jul;77(1):45-50
references.pmid: 7252257
references.citation: Dev Dyn. 2011 Aug;240(8):1949-57
references.pmid: 21761480
references.citation: Dev Biol. 2008 Jun 15;318(2):258-67
references.pmid: 18462713
references.citation: Nature. 2007 Nov 8;450(7167):285-8
references.pmid: 17994097
references.citation: Circulation. 2010 Mar 16;121(10):1256-63
references.pmid: 20231543
references.citation: Philos Trans A Math Phys Eng Sci. 2009 Sep 13;367(1902):3555-83
references.pmid: 19657011
references.citation: Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2473-81
references.pmid: 21963831
references.citation: Am J Physiol Heart Circ Physiol. 2001 Apr;280(4):H1547-59
references.pmid: 11247765
references.citation: Ultrasound Obstet Gynecol. 1999 Jun;13(6):437-45
references.pmid: 10423809
references.citation: Hypertension. 1996 Mar;27(3 Pt 2):799-803
references.pmid: 8613243
references.citation: Cardiology. 1975;60(1):4-49
references.pmid: 126799
references.citation: Development. 1998 Oct;125(19):3809-20
references.pmid: 9729489
references.citation: Science. 1991 Nov 22;254(5035):1178-81
references.pmid: 1957169
references.citation: Anat Embryol (Berl). 1995 May;191(5):415-23
references.pmid: 7625612
references.citation: Med Biol Eng Comput. 2008 May;46(5):479-84
references.pmid: 18228072
references.citation: Dev Dyn. 2004 May;230(1):57-68
references.pmid: 15108309
references.citation: Arterioscler Thromb Vasc Biol. 1999 Jun;19(6):1499-505
references.pmid: 10364081
references.citation: Anat Rec. 2000 Jul 1;259(3):248-62
references.pmid: 10861359
references.citation: Cardiovasc Res. 1999 Jan;41(1):87-99
references.pmid: 10325956
references.citation: J Magn Reson Imaging. 1992 Mar-Apr;2(2):237-40
references.pmid: 1562778
references.citation: Bioconjug Chem. 1993 Mar-Apr;4(2):105-11
references.pmid: 7873641
references.citation: Fed Proc Transl Suppl. 1965 Sep-Oct;24(5):815-20
references.pmid: 5214584
references.citation: Ann Biomed Eng. 2009 Jun;37(6):1069-81
references.pmid: 19337838
references.citation: Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1919-26
references.pmid: 16648183
references.citation: Anat Rec. 1993 Feb;235(2):261-74
references.pmid: 8420394
references.citation: Cardiovasc Eng Technol. 2011 Mar;2(1):35-47
references.pmid: 22448203
references.citation: Folia Morphol (Praha). 1969;17(2):102-36
references.pmid: 5770329
references.citation: J Biomech. 2001 Jan;34(1):121-4
references.pmid: 11425071
references.citation: Circulation. 2011 Feb 1;123(4):e18-e209
references.pmid: 21160056
references.citation: Science. 1986 Jan 24;231(4736):405-7
references.pmid: 3941904
references.citation: Pediatr Res. 1993 Jul;34(1):44-6
references.pmid: 8356017
references.citation: Dev Dyn. 2011 Jul;240(7):1670-80
references.pmid: 21604321
references.citation: J Exp Biol. 2005 May;208(Pt 10):1877-85
references.pmid: 15879068
references.citation: Biorheology. 2011;48(5):305-21
references.pmid: 22433571
references.citation: J Theor Biol. 1996 Jun 21;180(4):343-57
references.pmid: 8776466
references.citation: BMC Dev Biol. 2006 Nov 01;6:51
references.pmid: 17078885
references.citation: Phys Biol. 2008 Apr 10;5(1):015009
references.pmid: 18403831
references.citation: Circ Res. 2004 Nov 26;95(11):1109-17
references.pmid: 15528466