title: Developmental programming: maternal hypercholesterolemia and immunity influence susceptibility to atherosclerosis.
abstract: It is increasingly recognized that the in utero environment is an important determinant of adult disease, and extensive epidemiological evidence links dysmetabolic conditions during pregnancy with increased hypertension, cardiovascular disease, and diabetes later in life. The original Barker Hypothesis focused on low birth weight as the primary indicator of postnatal risk, but low birth weight may arise from other, non-metabolic conditions. This has impeded the identification of developmental programming mechanisms. More recently, the focus has shifted to the impact of specific maternal risk factors, such as obesity, metabolic syndrome, and diabetes, on cardiovascular risk in offspring. Inflammation plays a central role in these maternal conditions as well as in offspring atherogenesis, and two key factors that influence inflammation, maternal hypercholesterolemia and maternal immune mechanisms, have been shown to affect the developmental programming of atherosclerosis. Maternal hypercholesterolemia in pregnancy, even if only temporary, is associated with increased fatty streak formation in human fetal arteries and accelerated progression of atherosclerosis in normocholesterolemic children. Conversely, immunization of experimental animals with oxidized low-density lipoprotein cholesterol, an antigen prevalent in atherosclerotic lesions, inhibits the progression of atherosclerosis in the offspring of hypercholesterolemic mothers. These findings indicate it is possible, in principle, to program postnatal immune responses and to reduce atherosclerosis, and potentially other immunomodulated diseases, by targeted maternal immunomodulation.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093-0682, USA. wpalinski@ucsd.edu
authors.forename: Wulf
authors.initials: W
authors.lastname: Palinski
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Stefan
authors.initials: S
authors.lastname: Freigang
authors.forename: Claudio
authors.initials: C
authors.lastname: Napoli
mesh_terms: D050197:Atherosclerosis / Q000453:epidemiology / Q000209:etiology*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications*; D008431:Maternal-Fetal Exchange; D009752:Nutritional Status; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular; D011297:Prenatal Exposure Delayed Effects