title: Vascular dysfunction in children conceived by assisted reproductive technologies: underlying mechanisms and future implications.
abstract: Epidemiological studies in humans have demonstrated a relationship between pathological events during fetal development and increased cardiovascular risk later in life and have led to the so called "Fetal programming of cardiovascular disease hypothesis". The recent observation of generalised vascular dysfunction in young apparently healthy children conceived by assisted reproductive technologies (ART) provides a novel and potentially very important example of this hypothesis. This review summarises recent data in ART children demonstrating premature subclinical atherosclerosis in the systemic circulation and pulmonary vascular dysfunction predisposing to exaggerated hypoxia-induced pulmonary hypertension. These problems appear to be related to the ART procedure per se. Studies in ART mice demonstrating premature vascular aging and arterial hypertension further demonstrate the potential of ART to increase cardiovascular risk and have allowed to unravel epigenetic alterations of the eNOS gene as an underpinning mechanism. The roughly 25% shortening of the life span in ART mice challenged with a western style high-fat-diet demonstrates the potential importance of these alterations for the long-term outcome. Given the young age of the ART population, data on cardiovascular endpoints will not be available before 20 to 30 years from now. However, already now cohort studies of the ART population are needed to early detect cardiovascular alterations with the aim to prevent or at least optimally treat cardiovascular complications. Finally, a debate needs to be engaged on the future of ART and the consequences of its exponential growth for public health.
authors: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors: Stefano F
authors: SF
authors: Rimoldi
authors: Botnar Centre for Extreme Medicine, Department of Internal Medicine, University Hospital, Lausanne.
authors: Claudio
authors: C
authors: Sartori
authors: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors: Emrush
authors: E
authors: Rexhaj
authors: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors: David
authors: D
authors: Cerny
authors: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors: Robert
authors: R
authors: Von Arx
authors: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors: Rodrigo
authors: R
authors: Soria
authors: Centre de Procréation Médicalement Assistée, Lausanne, Switzerland.
authors: Marc
authors: M
authors: Germond
authors: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland.
authors: Yves
authors: Y
authors: Allemann
authors: Department of Cardiology and Clinical Research, Inselspital, University Hospital, Bern, Switzerland; Facultad de Ciencias, Departamento de Biología, Universidad de Tarapacá, Arica, Chile.
authors: Urs
authors: U
authors: Scherrer
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000196:embryology* / Q000235:genetics*; D002648:Child; D019175:DNA Methylation; D004730:Endothelium, Vascular / Q000196:embryology / Q000503:physiopathology*; D044127:Epigenesis, Genetic; D047109:Fetal Development; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*
chemical_list: D052250:Nitric Oxide Synthase Type III