Institute for Clinical and Translational Science
Growth Inhibition and Compensation in Response to Neonatal Hypoxia in Rats
- Author(s): Radom-Aizik, Shlomit
- Zaldivar, Frank P.
- Nance, Dwight M.
- Haddad, Fadia
- Cooper, Dan M.
- Adams, Gregory R.
- et al.
Published Web Locationhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737398/pdf/nihms447494.pdf
Hypoxia is an important disease mechanism in prematurity, childhood asthma and obesity. In children, hypoxia results in chronic inflammation.Methods
We investigated the effects of hypoxia (Hx) (12% O2) during postnatal day 2 to 20 in rats. Control groups were normoxic (Nc), and normoxic growth restricted (14 pup liters) (Gr).Results
Hypoxia decreased growth similar Gr. Hx increased plasma TNFα and IL-6 and decreased IGF-I and VEGF. Hypoxia resulted in right ventricular (RV) hypertrophy but disproportionate decrements in limb skeletal muscle (SM) growth. miR206 was depressed in the hypertrophied RV of Hx rats while increased in growth retarded SM. Hx resulted in a decreased RV mRNA for myostatin but had no effect on SM myostatin. The mRNA for hypoxia sensitive factors such as HIFα was depressed in the RV of Hx rats suggesting negative feedback.Conclusion
The results indicate that Hx induces a proinflammatory state that depresses growth regulating mechanisms and that tissues critical for survival, such as the heart, can escape from this general regulatory program to sustain life. This study identifies accessible biomarkers for evaluating the impact of interventions designed to mitigate the long-term deleterious consequences of hypoxia that all too often occur in babies born prematurely.