Increased vascularization VEGF and HIF-1 expression in myocardium of chronically anemic fetal sheep

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

Research output: Contribution to journalArticlepeer-review

Abstract

In chronic fetal anemia there is an increase in cardiac mass and cardiac output that is sufficient to maintain systemic tissue oxygenation. Cardiac output increases by 50%, myocardial blood flow increases five fold and cardiac hypertrophy occurs as the heart/body weight ratio increases 30%. To investigate the role of hypoxia inducible factor-1, an activator of vascular endothelial growth factor transcription in coronary vascular growth we measured VEGF, HIF-1 and capillary morphometry in fetal sheep at ∼130 d gestation made chronically anemic by daily isovolemic hemorrhage for 6 d. Compared to controls the hematocrit was reduced from 353±1.5 to 14.8±0.7%. Minimal capillary diameter increased in both the left (3.9±0.1 vs 5.5±0.5μm) and right ventricle (4.5±0.1 vs 7.1±0.4μm, means±se, n=5). The intercapillary distance, decreased in both the left (7.3±0.5 vs 5.5±0.4μm) and right ventricle (8.1±0.2 vs 5.5±0.4μm) and capillary density increased in the right ventricle (8.7±0.4 vs 10.4±0.6 103/mm2). Compared to controls, in extracts of anemic hearts, VEGF protein increased 4.5 fold (p<.001), VEGF mRNA increased 3.2 fold (p=.004), HIF-1α protein increased 3.8 fold (p=0.002), and HIF-1β protein increased 1.78 fold (p=.08, n=6). These results provide evidence for a molecular pathway by which anemia/hypoxia may increase coronary capillary growth.

Original languageEnglish (US)
Pages (from-to)A256
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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