title: Systemic maternal inflammation and neonatal hyperoxia induces remodeling and left ventricular dysfunction in mice.
abstract: OBJECTIVE
  The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood.
  
  
  RESULTS
  Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O(2) for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O(2) than in saline/RA mice. Isolated cardiomyocytes from LPS/O(2) mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O(2) mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O(2) mice.
  
  
  CONCLUSIONS
  These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health.
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, The Ohio State University, Columbus, Ohio, United States of America. Markus.Velten@NationwideChildrens.org
authors.forename: Markus
authors.initials: M
authors.lastname: Velten
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Hutchinson
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Gorr
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Lucchesi
authors.forename: Lynette K
authors.initials: LK
authors.lastname: Rogers
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000502:physiology; D002478:Cells, Cultured; D017630:Connexins / Q000378:metabolism; D004452:Echocardiography; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology; D018496:Hyperoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D008285:Major Histocompatibility Complex / Q000502:physiology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D024723:Ventricular Myosins / Q000378:metabolism
chemical_list: D017630:Connexins; D042461:Vascular Endothelial Growth Factor A; C081624:connexin 42; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D024723:Ventricular Myosins