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66: Obesity alters pregnancy-related maternal cardiovascular remodeling through a miR-29 related mechanism

      Objective

      Adequate local (spiral arteries) and systemic cardiovascular system (CVS) remodeling is the key to successful adaptation to pregnancy. Maternal obesity (MO) is a major risk factor for pre-eclampsia (PE), fetal growth restriction (FGR) and is associated with decreased CVS compliance through a yet to be determined mechanism. The miR-29 microRNA family is a powerful regulator of at least 16 extracellular matrix genes involved in CVS remodeling. Vascular miR-29 expression is decreased in FGR in humans and in overfed non-human primates and its placental expression is increased in patients with PE. The goal of this study was to evaluate CVS miR-29 (subgroups a, b, and c) and elastin expressions in MO. We hypothesized that MO would increase miR-29 and decrease elastin (ELN) mRNA expression in maternal heart.

      Study Design

      Three groups of baboons (Papio spp.) were studied: non-pregnant (two obese, two non-obese, NP, n=4), pregnant obese (POb,n=4), and pregnant non-obese (PnOb,n=4). The tissues (left ventricle (LV), left atrium (LA), aortic arch) were collected at the end of gestation (0.92G). ELN and miR-29 expressions were quantified by qRT-PCR. miR-29 RNA expression was analyzed using the formula: 2ΔtmiRNA 21-ΔtU6. Statistical analyses were performed with ANOVA and significance was set at p<0.05.

      Results

      LA miR-29 (a, c) expressions were lower in POb compared to the PnOb baboons (Fig. A), while in the LV miR-29b expression was higher (Fig. B). The expression of ELN was decreased in the LA and LV of POb compared to PnOb baboons (Fig. C) .

      Conclusion

      This is the first report documenting differential regulation of miR-29 family by MO. The ELN expression in the LV, paralleling changes in the miR-29, is in agreement with published data, which documented dramatic increase of ELN with the suppression of miR 29 in experimental models. Pharmacological tissue-specific targeting of miR-29 might represent a pioneering strategy for prevention and treatment of complications of MO, including PE.
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