Effect of Inflammation in Pregnancy on Maternal and Offspring Cardiovascular Systems

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Toews, Alexa
Pregnancy , Pregnancy complications , Cardiovascular disease , Inflammation , Maternal health , Offspring health , Developmental origins of health and disease
Complications of pregnancy are often characterised by abnormal inflammation during gestation and are associated with an increased risk of future maternal and offspring cardiovascular disease (CVD). Murine studies have revealed that inflammatory pregnancies are associated with the acquisition of risk factors for CVD, but not overt disease. Therefore, a second inflammatory stimulus, such as one induced by a high fat diet, may be necessary to produce overt dysfunction. This study utilized rodent models of pregnancy loss and fetal growth restriction to assess the effects of aberrant inflammation during pregnancy and subsequent high fat diet consumption on cardiac function, morphology, and biomarkers of CVD in mothers and offspring. In the maternal study, pregnant C57BL/6 mice were injected intraperitoneally (i.p.) with lipopolysaccharide (LPS, 50 µg/kg) to induce complete fetal loss on gestational day (GD) 10.5. Fourteen days later, mothers were transitioned to a high fat diet (60% kcal from fat) for 10 weeks. In the offspring study, pregnant Wistar rats were injected i.p. with low dose LPS (10 µg/kg) on GD 13.5 and higher dose LPS (40 µg/kg) on GDs 14.5-16.5 to induce growth restriction. Offspring were weaned at postnatal day 21 and transitioned to the high fat diet for 13 weeks. Echocardiography was used to assess cardiac function. At euthanasia, hearts were collected for histological assessment. Maternal cardiac blood was collected to assess CVD biomarkers. In the maternal model, we saw slight alterations in some parameters of cardiac function, morphology, and biomarkers of CVD. In the offspring model, males that were not growth restricted but were fed a high fat diet post-weaning had significantly altered systolic and diastolic function. Males on the high fat diet, regardless of in utero exposure to inflammation, also had significantly smaller hearts. Results from the maternal study may reflect early development of cardiovascular disease. The offspring model has raised questions regarding the influence of in utero inflammation and high fat diet consumption on cardiac development and subsequent function. Future studies with a longer timeline may further elucidate how these factors influence cardiac function and disease progression in mothers and offspring following a complicated pregnancy.
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