title: Chronic reduction in cardiac output induces hypoxic signaling in larval zebrafish even at a time when convective oxygen transport is not required.
abstract: In the present study, the zebrafish breakdance mutant (bre) was used to assess the role of blood flow in development because it has been previously shown that bre larvae have a chronically reduced cardiac output as a result of ventricular contraction following only every second atrial contraction in addition to an atrial bradycardia. We confirmed a 50% reduction compared with control fish and further showed that blood flow in the caudal part of the dorsal aorta decreased by 80%. Associated with these reductions in blood flow were indications of developmental retardation in bre mutants, specifically delayed hatching, reduced cell proliferation, and a transiently decreased growth rate. Surprisingly, an increased red blood cell concentration and an earlier appearance of trunk vessels in bre larvae indicated some compensation to convective oxygen transport, although in previous studies it has been shown that zebrafish larvae at this stage obtain oxygen by bulk diffusion. In bre animals immunohistochemical analyses showed a significant increase in hypoxia inducible factor 1 (HIF)-α protein expression, comparable with wild-type larvae that were raised under hypoxic conditions. Accordingly, the expression of some hif downstream genes was affected. Furthermore, Affymetrix microarray analyses revealed a large number of genes that were differently expressed comparing control and bre larvae, and the number even increased with proceeding development. The results showed that a chronic reduction in blood flow generated hypoxic molecular signals despite partial compensation by increased oxygen carrying capacity and transiently slowed the overall development of zebrafish bre larvae.
authors.affiliation: Institute of Zoology and Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria. Renate.Kopp@uibk.ac.at
authors.forename: Renate
authors.initials: R
authors.lastname: Kopp
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schwerte
authors.forename: Margit
authors.initials: M
authors.lastname: Egg
authors.forename: Adolf Michael
authors.initials: AM
authors.lastname: Sandbichler
authors.forename: Bernhard
authors.initials: B
authors.lastname: Egger
authors.forename: Bernd
authors.initials: B
authors.lastname: Pelster
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D056926:CLOCK Proteins / Q000235:genetics; D002302:Cardiac Output / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D056744:Cyclin B1 / Q000235:genetics; D004921:Erythropoietin / Q000235:genetics; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007814:Larva / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D056744:Cyclin B1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D029961:Zebrafish Proteins; C523494:epoa protein, zebrafish; D004921:Erythropoietin; D056926:CLOCK Proteins; D010100:Oxygen