Perinatal Inflammation Results in Sex-Dependent Cardiac Dysfunction

Area of Science:

• Cardiovascular Biology
• Neonatal Physiology
• Developmental Origins of Health and Disease

Background:

• Preterm birth and fetal growth restriction are linked to adult heart failure.
• Adverse maternal environments contribute to poor fetal development and preterm birth.
• Neonatal hyperoxia is often required for premature infants with immature lungs.

Purpose of the Study:

• To test if early-life cardiac structural protein changes predict adult cardiac dysfunction.
• To investigate sex-dependent differences in cardiac adaptation to early-life insults.

Main Methods:

• Utilized a murine model of maternal inflammation (lipopolysaccharide) and neonatal hyperoxia.
• Assessed cardiac structural proteins (alpha-myosin heavy chain) and left ventricular function.
• Examined sex-specific pathological changes at 10 months of age.

Main Results:

• Female mice showed transient decreases in alpha-myosin heavy chain (αMHC) expression post-inflammation.
• Male mice exposed to inflammation and hyperoxia exhibited delayed but significant increases in αMHC.
• Left ventricular function correlated with protein changes, with males displaying a more severe cardiac phenotype.

Conclusions:

• Early alterations in cardiac contractile proteins are temporally linked to cardiac dysfunction.
• Male mice demonstrated a more severe sex-dependent cardiac adaptation.
• Findings suggest potential predictive value for heart disease risk in growth-restricted human infants.