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
| Autor: | D. Kimberly, A. Y. Yu, G. L. Semenza, A. R. Hohimer, C. Martin, Bing-Hua Jiang, Lowell E. Davis |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Cardiac output Diastole Cardiomegaly Endothelial Growth Factors Hematocrit Muscle hypertrophy chemistry.chemical_compound Internal medicine Coronary Circulation medicine Animals Humans Cardiac Output Cells Cultured Fetus Lymphokines Sheep medicine.diagnostic_test business.industry Vascular Endothelial Growth Factors Myocardium Helix-Loop-Helix Motifs Obstetrics and Gynecology Nuclear Proteins Anemia Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit Capillaries Vascular endothelial growth factor DNA-Binding Proteins Vascular endothelial growth factor A Fetal Diseases Endocrinology chemistry Chronic Disease Female Hypoxia-Inducible Factor 1 medicine.symptom business Transcription Factors |
| Zdroj: | American journal of obstetrics and gynecology. 178(3) |
| ISSN: | 0002-9378 |
| Popis: | 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 age-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. (Am J Obstet Gynecol 1998;178:527-34.) |
| Databáze: | OpenAIRE |
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