Author + information
- Received April 28, 2017
- Revision received August 4, 2017
- Accepted August 23, 2017
- Published online October 17, 2018.
- Maria Angela Guzzardi, PhDa,
- Tiziana Liistro, PhDa,
- Luna Gargani, MD, PhDa,
- Lamia Ait Ali, MD, PhDa,
- Gennaro D’Angelo, RNa,
- Silvia Rocchiccioli, PhDa,
- Federica La Rosa, BSca,
- Alessandra Kemeny, MDb,
- Elena Sanguinetti, PhDa,c,
- Nadia Ucciferri, PhDa,
- Mariarosaria De Simone, PhDa,
- Antonietta Bartoli, PhDa,
- Pierluigi Festa, MDd,
- Piero A. Salvadori, MSca,
- Silvia Burchielli, DVMd,
- Rosa Sicari, MD, PhDa and
- Patricia Iozzo, MD, PhDa,∗ ()
- aInstitute of Clinical Physiology, National Research Council, Pisa, Italy
- bGynaecology and Obstetrics Department, Azienda USL Toscana Nord Ovest, Massa e Carrara, Italy
- cScuola Superiore di Studi Universitari e di Perfezionamento S. Anna, Pisa, Italy
- dFondazione Toscana Gabriele Monasterio, Pisa, Italy
- ↵∗Address for correspondence:
Dr. Patricia Iozzo, Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, 56124 Pisa, Italy.
Objectives The aim of this study was to investigate the consequences of maternal overweight on cardiac development in offspring in infants (short term) and minipigs (short and longer term).
Background The epidemic of overweight involves pregnant women. The uterine environment affects organ development, modulating disease susceptibility. Offspring of obese mothers have higher rates of cardiovascular events and mortality.
Methods Echocardiography was performed in infants born to lean and overweight mothers at birth and at 3, 6, and 12 months of age. In minipigs born to mothers fed a high-fat diet or a normal diet, cardiac development (echocardiography, histology), glucose metabolism and perfusion (positron emission tomography), triglyceride and glycogen content, and myocardial enzymes regulating metabolism (mass spectrometry) were determined from birth to adulthood.
Results In neonates, maternal overweight, especially in the last trimester, predicted a thicker left ventricular posterior wall at birth (4.1 ± 0.3 vs. 3.3 ± 0.2 mm; p < 0.05) and larger end-diastolic and stroke volumes at 1 year. Minipigs born to mothers fed a high-fat diet showed greater left ventricular mass (p = 0.0001), chambers (+100%; p < 0.001), stroke volume (+75%; p = 0.001), cardiomyocyte nuclei (+28%; p = 0.02), glucose uptake, and glycogen accumulation at birth (+100%; p < 0.005), with lower levels of oxidative enzymes, compared with those born to mothers fed a normal diet. Subsequently, they developed myocardial insulin resistance and glycogen depletion. Late adulthood showed elevated heart rate (111 ± 5 vs. 84 ± 8 beats/min; p < 0.05) and ejection fraction and deficient fatty acid oxidative enzymes.
Conclusions Neonatal changes in cardiac morphology were explained by late-trimester maternal body mass index; myocardial glucose overexposure seen in minipigs can justify early human findings. Longer term effects in minipigs consisted of myocardial insulin resistance, enzymatic alterations, and hyperdynamic systolic function.
- cardiac triglycerides
- developmental programming
- glucose metabolism
- positron emission tomography
This research was funded by the European Commission under the Seventh Framework Programme (FP7-HEALTH-DORIAN Project: Developmental Origins of Healthy and Unhealthy Ageing: The Role of Maternal Obesity; grant 278603) and the European Foundation for the Study of Diabetes (EFSD/Roche Educational Grant 2009). The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Guzzardi and Liistro contributed equally to this work and are joint first authors.
- Received April 28, 2017.
- Revision received August 4, 2017.
- Accepted August 23, 2017.
- 2018 American College of Cardiology Foundation
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