Effects of perinatal, late foetal, and early embryonic insults on the cardiovascular phenotype in experimental animal models and humans.
Cardiovascular diseases are the main cause of mortality and morbidity in Western countries, but the underlying mechanisms are still poorly understood. Genetic polymorphisms, once thought to represent a major determinant of cardiovascular risk, individually and collectively, only explain a tiny fraction of phenotypic variation and disease risk in humans. It is now clear that non-genetic factors, i.e., factors that modify gene activity without changing the DNA sequence and that are sensitive to the environment can cause important alterations of the cardiovascular phenotype in experimental animal models and humans. Here, we will review recent studies demonstrating that distinct pathological events during the perinatal (transient perinatal hypoxemia), late foetal (preeclampsia), and early embryonic (assisted reproductive technologies) periods induce profound alterations of the cardiovascular phenotype in humans and experimental animals. Moreover, we will provide evidence that epigenetic modifications are contributing importantly to this problem and are conferring the potential for its transmission to subsequent generations.
1 University Hospital, Bern, Switzerland.
Theo Arthur
TA
Meister
1 University Hospital, Bern, Switzerland.
Emrush
E
Rexhaj
1 University Hospital, Bern, Switzerland.
Stefano Flavio
SF
Rimoldi
1 University Hospital, Bern, Switzerland.
Urs
U
Scherrer
2 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Claudio
C
Sartori
D000367:Age Factors; D000818:Animals; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000196:embryology / Q000209:etiology* / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D005311:Fetal Hypoxia / Q000150:complications* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D059647:Gene-Environment Interaction; D005865:Gestational Age; D006801:Humans; D010641:Phenotype; D011225:Pre-Eclampsia / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011379:Prognosis; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*; D012307:Risk Factors
ART; Cardiovascular risk; epigenetic; foetal programming; preeclampsia; vascular dysfunction