title: Time-Series Interactions of Gene Expression, Vascular Growth and Hemodynamics during Early Embryonic Arterial Development.
abstract: The role of hemodynamic forces within the embryo as biomechanical regulators for cardiovascular morphogenesis, growth, and remodeling is well supported through the experimental studies. Furthermore, clinical experience suggests that perturbed flow disrupts the normal vascular growth process as one etiology for congenital heart diseases (CHD) and for fetal adaptation to CHD. However, the relationships between hemodynamics, gene expression and embryonic vascular growth are poorly defined due to the lack of concurrent, sequential in vivo data. In this study, a long-term, time-lapse optical coherence tomography (OCT) imaging campaign was conducted to acquire simultaneous blood velocity, pulsatile micro-pressure and morphometric data for 3 consecutive early embryonic stages in the chick embryo. In conjunction with the in vivo growth and hemodynamics data, in vitro reverse transcription polymerase chain reaction (RT-PCR) analysis was performed to track changes in transcript expression relevant to histogenesis and remodeling of the embryonic arterial wall. Our non-invasive extended OCT imaging technique for the microstructural data showed continuous vessel growth. OCT data coupled with the PIV technique revealed significant but intermitted increases in wall shear stress (WSS) between first and second assigned stages and a noticeable decrease afterwards. Growth rate, however, did not vary significantly throughout the embryonic period. Among all the genes studied, only the MMP-2 and CASP-3 expression levels remained unchanged during the time course. Concurrent relationships were obtained among the transcriptional modulation of the genes, vascular growth and hemodynamics-related changes. Further studies are indicated to determine cause and effect relationships and reversibility between mechanical and molecular regulation of vasculogenesis.
authors.affiliation: Mechanical Engineering Department, Koc University, Istanbul, Turkey.
authors.forename: Selda
authors.initials: S
authors.lastname: Goktas
authors.affiliation: Mechanical Engineering Department, Koc University, Istanbul, Turkey.
authors.forename: Fazil E
authors.initials: FE
authors.lastname: Uslu
authors.affiliation: Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Kowalski
authors.affiliation: Mechanical Engineering Department, Koc University, Istanbul, Turkey.
authors.forename: Erhan
authors.initials: E
authors.lastname: Ermek
authors.affiliation: Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY, United States of America.
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Keller
authors.affiliation: Mechanical Engineering Department, Koc University, Istanbul, Turkey.
authors.forename: Kerem
authors.identifier: http://orcid.org/0000-0001-7637-4445
authors.initials: K
authors.lastname: Pekkan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001158:Arteries / Q000196:embryology* / Q000378:metabolism*; D001794:Blood Pressure; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002642:Chick Embryo; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006439:Hemodynamics / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000235:genetics; D033081:Shear Strength; D015398:Signal Transduction; D013314:Stress, Mechanical; D059008:Time-Lapse Imaging; D041623:Tomography, Optical Coherence; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta