A Gut Feeling About Developmental Programming Mechanisms

It is now widely recognized that perinatal exposure to maternal dysmetabolic conditions may influence cardiovascular diseases in offspring.1 Maternal hypercholesterolemia, in particular, increases the susceptibility to atherosclerosis in humans and experimental models. The translational relevance of developmental programming is obvious. If safe interventions in hypercholesterolemic mothers before or during pregnancy can attenuate pathogenic programming, atherogenesis may be reduced throughout adult life.1 Although the consequences of maternal hypercholesterolemia in humans are increasingly evident,2 the mechanisms involved remain largely unknown.See accompanying article on page 2053 this edition of the journal, Trenteseaux et al3 identify a novel mechanism that may promote atherosclerosis in apoE−/− mice. In their study, homozygous female offspring of hypercholesterolemic (apoE−/−) mothers developed greater lesions in the aortic root than offspring of normocholesterolemic (apoE+/−) mothers, consistent with increased aortic atherosclerosis observed in LDL−/− mice or rabbits. Remarkably, maternal hypercholesterolemia was associated with higher plasma levels of trimethylamine-N-oxide …