Cardiac hypertrophy in chronically anemic fetal sheep: Increased vascularization is associated with increased myocardial expression of vascular endothelial growth factor and hypoxia-inducible factor 1

C. Martin, A. Y. Yu, B. H. Jiang, L. Davis, D. Kimberly, A. R. Hohimer, G. L. Semenza

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

OBJECTIVE: Our purpose was to determine whether the increase in fetal cardiac mass and cardiac output in chronic anemia is accompanied by changes in capillary density or size or changes in levels of vascular endothelial growth factor and hypoxia-inducible factor 1, a basic helix-loop-helix transcription factor that has previously been shown to activate vascular endothelial growth factor gene transcription when cultured cells are subjected to hypoxia. STUDY DESIGN: Anemia was induced in near-term ovine fetuses by daily isovolemic hemorrhage. In five fetuses the heart was arrested in diastole, isolated, and fixed at physiologic pressures with adenosine-paraformaldehyde, and morphometric measurements of capillaries were made. In six fetuses cardiac expression of vascular endothelial growth factor and hypoxia-inducible factor 1 protein was detected by Western analysis and vascular endothelial growth factor messenger ribonucleic acid by Northern blot analysis. Eleven ago-matched fetuses served as controls. RESULTS: The anemic fetuses compared with controls had a lower hematocrit (14.8% ± 0.7% vs 35.3% ± 1.5%) and a greater heart-to-body weight ratio (10.5 ± 1.1 vs 7.7 ± 0.5 gm/kg). The minimal capillary diameter was increased and the intercapillary distance was decreased in both right and left ventricles of anemic fetuses compared with controls. Vascular endothelial growth factor protein was increased 4.5-fold, vascular endothelial growth factor messenger ribonucleic acid 3.2-fold, and hypoxia-inducible factor 1α protein 3.8-fold in ventricular tissue from anemic fetuses. CONCLUSIONS: In chronic fetal anemia cardiac hypertrophy is accompanied by anatomic changes in myocardial capillary morphometry along with induction of hypoxia-inducible factor 1 and vascular endothelial growth factor. These results provide evidence for a pathway by which anemia-hypoxia may stimulate myocardial vascularization.

Original languageEnglish (US)
Pages (from-to)527-534
Number of pages8
JournalAmerican journal of obstetrics and gynecology
Volume178
Issue number3
DOIs
StatePublished - Jan 1 1998

Keywords

  • Anemia
  • Fetal heart
  • Hypoxia-inducible factor 1
  • Ovine
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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