Perinatal Programming of Cerebro-Cardiovascular Risk

It is now clearly established that perturbations of the environment (nutritional, hormonal, …) during critical periods of development can have a major impact on the health orientations of individuals in later life. This concept of «Developmental Origins of Health and Disease» covers the whole perinatal period (immediate pre- and post-natal) and is called «Programming». For example, during the period immediately after birth, the nutritional environment plays a key role in determining the future weight, metabolic and cardio-vascular orientations of the individual.

By using of experimental models  (rats, mice), our team aimed to elucidate the mechanisms and consequences of postnatal programming. Indeed, we showed that postnatal overfeeding (PNOF) induced an increase in body weight, an alteration of glucose-lipid metabolism and an increase in arterial blood pressure, characteristic components of metabolic syndrome. Concerning the cardio-vascular system, we showed that PNOF led to: early changes in cardiac gene expression, a progressive alteration of myocardial contractile function in vivo, an increase in nitro-oxidative stress, and an increase in sensitivity to ischemia-reperfusion lesions ex vivo.

The objective of the research project of this axis will be to answer the following questions:

• Does PNOF-related programming induce greater susceptibility to myocardial infarction, heart failure, and ischemic stroke in adulthood?
• What genes, cardiac  or cerebral, have their expression modified by PNOF and do these modifications occur early or late?
• Are these alterations reversible by an appropriate treatment: nutritional or pharmacological?