Impact du stress hyperoxique en période néonatale sur la structure vasculaire : implication des phénomènes de sénescence et rôle possible dans la programmation développementale de l'hypertension artérielle

Abstract : The scope of this thesis is developmental programming of arterial high blood pressure (HBP) hypertension through early neonatal stimuli that may alter vascular development. Premature newborns have decreased antioxidant defenses compared to term babies and are exposed upon birth to high oxygen (O2) concentration, causing reactive oxygen species (ROS) production. Long term vascular consequences of ROS related damage during the neonatal period and the mechanisms involved remain unknown. Recent data from the laboratory show that neonatal hyperoxic stress leads in adult rat to HBP, endothelial dysfunction and arterial rigidity, characteristic features of vascular aging. We hypothesize that a neonatal hyperoxic stress leads to long term vascular structure alteration explained by an early aging of the vascular system. We showed a decreased proliferation rate, an altered angiogenic capacity, as well as long term DNA damage and increased expression of senescence proteins at a vascular level following O2 exposure in the animal (male Sprague-Dawley pups kept at 80% O2 from postnatal days 3 to 10 vs. rats remained in room air) and cellular models (embryonic vascular smooth muscle cells from rat thoracic aorta exposed to 40% O2 for 24h or 48h followed by 96h recovery in control conditions). In addition, alterations of vascular structure components indicating vascular remodeling was shown before the onset of the HBP at adult age. Those changes precede the HBP and vascular dysfunction observed in our animal model at adult age and could contribute to them. Study of young adults born before 29 weeks vs. young adults born at term showed that young adults born preterm present indices of arterial stiffness vs. term controls. Results of the present thesis demonstrate a major role of premature vascular aging in the surge of vascular diseases in adulthood and contribute to a better understanding of the patho-physiological mechanisms involved and could put into practice new prevention strategies among preterm patients
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Fanny Huyard. Impact du stress hyperoxique en période néonatale sur la structure vasculaire : implication des phénomènes de sénescence et rôle possible dans la programmation développementale de l'hypertension artérielle. Médecine humaine et pathologie. Université de Lorraine, 2013. Français. ⟨NNT : 2013LORR0100⟩. ⟨tel-01750087⟩

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