Long-term exposure to high altitude hypoxia during pregnancy increases fetal heart susceptibility to ischemia/reperfusion injury and cardiac dysfunction.
Int J Cardiol
; 274: 7-15, 2019 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-30017521
ABSTRACT
BACKGROUND:
High altitude hypoxia (HAH) exposure affects fetal development. However, the fetal cardiovascular responses to the HAH are not well understood. We have tested the hypothesis that long-term HAH exposure alters the hypoxia/ischemia-sensitive gene expressions, leading to an increase in fetal heart susceptibility to ischemia/reperfusion (I/R) injury and cardiac dysfunction.METHODS:
Time-dated pregnant sheep were exposed to high-altitude (3820â¯m) or were maintained at sea level (~300â¯m) for 110â¯days. Fetal hearts were isolated from the near-term ewes and subjected to I/R in a Langendorff preparation.RESULTS:
HAH decreased the fetal body and heart weights in the female but not male fetuses. HAH had no effect on the left ventricle (LV) function at baseline, but increased the LV infarct size and attenuated the post-ischemic recovery of LV function in both male and female fetuses, as compared with the normoxic groups. HAH increased the protein levels of hypoxia-inducible factor (HIF)-1α and DNA methyltransferases type 3b (DNMT3b), but attenuated protein kinase C epsilon (PKCε) levels in the fetal hearts. AHA induced a 4.3 fold increase of miR-210 in the males and a 2.9 fold increase in female hearts. In addition, HAH had no effect on mTOR protein and phosphorylation levels but increased the autophagy biomarker, LC3B-II protein levels and LC3B-II/LC3B-I ratio in the fetal hearts.CONCLUSION:
The results suggest that gestational HAH exposure induces in utero programming of the hypoxia/ischemia-sensitive gene expression pattern in the developing heart and increases cardiac susceptibility to I/R injury.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Efectos Tardíos de la Exposición Prenatal
/
Preñez
/
Daño por Reperfusión Miocárdica
/
Función Ventricular Izquierda
/
Mal de Altura
/
Corazón Fetal
/
Hipoxia
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Int J Cardiol
Año:
2019
Tipo del documento:
Article
País de afiliación:
China