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Perinatal inflammation and oxidative stress induce fetal cardiac dysfunction
Author(s) -
Velten Markus,
Gorr Matthew W,
Youtz Dane Y,
Velten Christina,
Rogers Lynette K,
Wold Loren E
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1187.1
Subject(s) - phospholamban , contractility , medicine , endocrinology , inflammation , oxidative stress , offspring , cardiac function curve , heart failure , fetus , biology , pregnancy , genetics
Background Epidemiological data suggest that maternal inflammation contributes to intrauterine growth restriction, preterm birth, and adult‐onset cardiovascular diseases. Objective We hypothesize that perinatal inflammation and oxidative stress may induce discernible alterations in cardiomyocyte contractility and calcium signaling, causing cardiac dysfunction in the absence of subsequent risk factors. Methods Pregnant C3H/HeN mice were LPS or saline injected on embryonic day 16. Offspring were placed in room air or 85% O 2 for 14 days. In vivo echocardiography, in vitro cardiomyocyte function, protein, and RNA analyses were performed. Main Results LPS/O 2 exposed mice exhibited a compromised LV function and decrease in myocyte peak shortening and time‐to‐90% peak shortening. β‐MHC protein levels were increased and calcium transient amplitude was greatest in LPS/O 2 mice, a pattern observed in humans and animal models of heart failure. SERCA2a RNA and protein levels were increased and phospholamban mRNA levels were decreased in LPS/O 2 mice, a pattern observed during fetal development. Phosphorylation of phospholamban was increased, along with Sorcin mRNA levels. Conclusions Maternal inflammation and neonatal oxidative stress resulted in impaired cardiac contractility consistent with heart failure, with the fetal cardiac phenotype persistent during the postnatal stage.