Maternal obesity impairs fetal cardiomyocyte contractile function in sheep

Qiurong Wang, Chaoqun Zhu, Mingming Sun, Rexiati Maimaiti, Stephen P. Ford, Peter W. Nathanielsz, Jun Ren, Wei Guo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Obesity is a major public health problem worldwide. In the United States, one-third of women of reproductive age are obese. Human studies show that maternal obesity (MO) predisposes offspring to cardiovascular disease. However, the underlying mechanisms remain unclear. Given the similarities between pregnancy in sheep and humans,we studied sheep to examine the impact ofMOon fetal cardiomyocyte contractility at term. We observedthatMOimpaired cardiomyocyte contractilityby reducing peak shortening andshortening/relengthening velocity, prolonging time to relengthening. MO disrupted Ca2+ homeostasis in fetal cardiomyocytes, increasing intracellular Ca2+ and inducing cellular Ca2+ insensitivity. The Ca2+-release channelwas impaired, but Ca2+ uptake was unaffected byMO. The upstreamkinases that phosphorylate the Ca2+-release channel-ryanodine receptor-2, PKA, and calmodulin-dependent protein kinase II-were activated in MO fetuses. Contractile dysfunction was associated with an increased ratio of myosin heavy chain (MHC)-b to MHC-a and upregulated cardiac troponin (cTn)-T and tropomyosin, as well as cTn-I phosphorylation. In summary, this is the first characterization of the effects of MO on fetal cardiomyocyte contractility. Our findings indicate that MO impairs fetal cardiomyocyte contractility through altered intracellular Ca2+ handling, overloading fetal cardiomyocyte intracellular Ca2+ and aberrantmyofilament protein composition. Thesemechanisms may contribute to developmental programming by MOof offspring cardiac function and predisposition to later life cardiovascular disease in the offspring.

Original languageEnglish (US)
Pages (from-to)2587-2598
Number of pages12
JournalFASEB Journal
Volume33
Issue number2
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Ca sensitivity
  • Cardiac programming
  • Myofilament

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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