Increased systolic load causes adverse remodeling of fetal aortic and mitral valves

Frederick A. Tibayan, Samantha Louey, Sonnet Jonker, Herbert Espinoza, Natasha Chattergoon, Fanglei You, Kent L. Thornburg, George Giraud

    Research output: Contribution to journalArticlepeer-review

    1 Scopus citations


    While abnormal hemodynamic forces alter fetal myocardial growth, little is known about whether such insults affect fetal cardiac valve development. We hypothesized that chronically elevated systolic load would detrimentally alter fetal valve growth. Chronically instrumented fetal sheep received either a continuous infusion of adult sheep plasma to increase fetal blood pressure, or a lactated Ringer’s infusion as a volume control beginning on day 126 ± 4 of gestation. After 8 days, mean arterial pressure was higher in the plasma infusion group (63.0 mmHg vs. 41.8 mmHg, P < 0.05). Mitral annular septal-lateral diameter (11.9 mm vs. 9.1 mm, P < 0.05), anterior leaflet length (7.7 mm vs. 6.4 mm, P < 0.05), and posterior leaflet length (P2; 4.0 mm vs. 3.0 mm, P < 0.05) were greater in the elevated load group. mRNA levels of Notch-1, TGF-β2, Wnt-2b, BMP-1, and versican were suppressed in aortic and mitral valve leaflets; elastin and α1 type I collagen mRNA levels were suppressed in the aortic valves only. We conclude that sustained elevated arterial pressure load on the fetal heart valve leads to anatomic remodeling and, surprisingly, suppression of signaling and extracellular matrix genes that are important to valve development. These novel findings have important implications on the developmental origins of valve disease and may have long-term consequences on valve function and durability.

    Original languageEnglish (US)
    Pages (from-to)R1490-R1498
    JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
    Issue number12
    StatePublished - 2015


    • Animal model
    • Fetus
    • Heart development
    • Heart valve
    • Mechanical load

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)


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