Prenatal exposure to maternal obesity and SFLT-1 overexpression and cardiovascular function in the adult offspring

Date

2010-03-11

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Abstract

Cardiovascular disease is the leading cause of death in the United States. Adult smoking, type II diabetes, and other environments and conditions, have been identified as risk factors for cardiovascular diseases; however, the effects of prenatal development cannot be overlooked. In the 1980s Barker proposed a hypothesis that poor nutrition in the fetal or early neonatal period increases susceptibility to the negative effects of an affluent diet during adulthood. Overall, there is little understanding of the exact mechanisms of the developmental origin of adult disease, but it is recognized that adult disease occur when postnatal environment is considerable different from what fetus experienced while in utero. The obesity epidemic has led to the evaluation of the effect of a high fat nutritional environment on fetal programming. Conversely, recent studies have shown that the maternal prepregnancy weight is a strong independent risk factor for preeclampsia. Preeclampsia by itself has a negative effect on offspring’s future cardiovascular function. It is possible that maternal obesity in conjunction with preeclampsia may emerge as one of the risk for impairment of cardiovascular function in adult life. \r\nThese studies were performed to determine the effect of prepregnancy obesity and sFlt1-induced preeclampsia on cardiovascular function in the offspring in a small animal model. A link between increased blood pressure and amplified vascular reactivity was revealed in offspring born to mothers fed high fat diet and with or without sFlt1 overexpression during pregnancy. In addition, investigation of metabolic, inflammatory and atherosclerotic profiles and determination protein expressions of angiotensin II, as well as its receptors, lead to a conclusion that maternal obesity is a much stronger negative factor influencing offspring’s cardiovascular function than pregnancy complications. Though, if combined together, obesity and preeclampsia have even more detrimental effect. Study also identified possible mechanisms and indicated several directions for therapeutical approaches. \r\n

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Keywords

vascular reactivity, mice, fetal programming

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