Perinatal inflammation Causes Adult Cardiac Diseases A Novel Model for Fetal Origins of Adult Diseases

Aims Epidemiological studies have described an impact of the fetal environment on cardiovascular mortality at adulthood. However, the pathogenic mechanisms of this fetal programming remain to be elucidated. Systemic maternal inflammation is a common health‐threat affecting the developing fetus, causing preterm birth. Preterm infants often require oxygen therapy. We hypothesized that perinatal inflammation and neonatal hyperoxia exposure alters cardiac structure and function during adulthood Methods Pregnant C3H/HeN mice were E16 LPS or saline injected. Offspring were placed in room air (RA) or 85% O2 for 14 days and subsequently raised in RA to 8 wks. Results Echocardiography revealed a reduced EF and increased LV end systolic diameter in LPS/O2 mice. Isolated myocytes form LPS/O2 mice had a slower shortening and relengthening, and a slower return to baseline than controls. Each single insult increased α‐MHC protein expression., while LPS decreased β‐MHC expression. SERCA2a and desmin levels were increased, and connexin 43 was decreased in LPS/O2‐exposed mice. Significance We conclude that in mice, LPS/O2 reduces connexin 43, alters Ca2+ signaling, and impairs myocyte contractility, thereby promoting the development of cardiac dysfunction. These findings suggest that this model maybe a useful to elucidate in perinatal mechanisms of adult cardiac diseases. Funding: DFG 614/1‐1, AHA 0830241N