Review: The Placenta is a Programming Agent for Cardiovascular Disease
Introduction
Across the globe, far more people die of cardiovascular disease than any other disease in spite of the decline in cardiovascular related deaths since the early 1970s. Nevertheless, the annual cost of cardiovascular disease continues to increase in the US and is expected to reach the half trillion dollar mark next year. This continual rise in cost is due in part to the increase in the numbers of people with myocardial damage who now progress to heart failure. Heart failure is the fastest growing reason for hospitalization in the US, and the most expensive. An additional dark cloud sits on the horizon. An increasing number of children and adolescents are gaining excessive body weight and crossing the health threshold into the realm of chronic disease. This portends a further increase in health care costs in the coming decades as increasing numbers of middle aged adults with type 2 diabetes and coronary heart disease require medical attention [1]. Medical scientists are wondering how this epidemic of metabolic disease evolved and how it might be stopped. There is reason to believe that a better understanding of early human development might shed light on the problem.
Section snippets
Programming of cardiovascular disease
Twenty years ago David Barker and colleagues showed that mortality due to ischemic heart disease increased with decreasing birthweights over the 5 to 9 pound (2.3–4.1 kg) range; in addition, they found that babies at the largest end of the birthweight scale, above 9.5 pounds (4.3 kg), also had high rates of mortality [2]. Thus it appears that babies at both ends of the birthweight spectrum are at high risk for cardiovascular disease in adulthood. Over the intervening 20 years, a number of human
The placenta and cardiovascular disease: data from the Helsinki Birth Cohorts
The Helsinki Birth Cohorts have been especially helpful in uncovering the relationships between placental size and shape, and cardiovascular diseases in later life. Two primary Helsinki Birth Cohorts have been studied: men and women born between 1924 and 1933, and a younger cohort born between 1934 and 1944. Data from these cohorts are highly valuable because they contain information regarding birth size, placental size, childhood growth and health records. The team of Johann Eriksson, Eero
Fetal cardiac development is vulnerable to placental vascular development
The heart must grow in capacity throughout gestation to provide sufficient blood flow for growing fetal organs. Thus, the fractional cardiac output that supplies the placenta remains constant, at least over the last half of gestation [11]. Increases in placental flow impedance, as found in placental insufficiency, lead to adjustments in growth by the embryonic and fetal heart. This is understandable because the heart must eject against the instantaneous resistance of the placental bed, the
Placental insufficiency
Most of our understanding of the biological mechanisms that underpin placental insufficiency has come from animal models. The functional surface area of the sheep placenta can be reduced by various means including umbilical arterial embolization with microspheres or by carunclectomy. The first method produces placental insufficiency by infusion of 50 μm mucopolysaccharide microspheres into the umbilico-placental circulation; embolization causes umbilical blood flow to decrease as placental
The placenta is the link between maternal nutrition, fetal growth and cardiovascular disease risk
Human and animal studies have consistently shown that maternal diet during pregnancy has a profound impact on fetal growth and future risk of chronic disease. Children born to poorly nourished (including high protein and fat intake) mothers have a significantly higher incidence of coronary heart disease and hypertension in adulthood [27], [28]. As mentioned above, recent studies from the Helsinki Birth Cohort demonstrate that placental size and shape, conditioned by maternal height, are also
Future directions
Despite several decades of materno-feto-placental studies, many fundamental questions remain unanswered. We know that as the interface between mother and fetus, the placenta is critical for normal fetal growth and development but the mechanisms underlying the placental origins of adult cardiovascular disease in offspring remain unclear. A thorough investigation of maternal influences on placental development (both at the time of implantation and throughout pregnancy) in addition to the specific
Conflict of interest statement
All authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work.
Acknowledgements
This research at Oregon Health and Science University was supported by the National Institute of Child Health and Human Development Program Project Grant (P01HD34430), Fellowships by the American Heart Association (Louey and O'Tierney) and the M. Lowell Edwards Endowment (Thornburg).
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