Hypertension pulmonaire associée à la dysplasie broncho-pulmonaire du nouveau-né prématuré : état actuel des connaissances et étude de l’intérêt du célastrol

Abstract : Introduction: bronchopulmonary dysplasia is a common pathology of premature newborns caused by oxidative stress and mechanical ventilation in these immature lungs, resulting in hypoalveolization and impaired angiogenesis. It can be complicated by pulmonary hypertension (HTP-DBP), and then right heart failure associated with excess mortality at 2 years of age. Celastrol has anti-inflammatory and antioxidant properties. Futhermore, in a murine model of systemic hypertension, it decreases systemic blood pressure and inhibits vascular remodeling and myocardial hypertrophy by attenuating inflammation and oxidative stress in vascular smooth muscle cells (VSMCs). It is therefore a molecule of choice for the study of a preventive treatment of HTP-DBP. Materials/Methods: we studied the influence of celastrol in a murine model of hyperoxic HTP-DBP by evaluating survival, HTP with measurement of pulmonary artery acceleration time (PAAT), right vascular remodeling, alveolization as well density, vascular reactivity and remodeling. We also evaluated the calcium response of fetal pulmonary VSMCs. Results: celastrol reduces mortality at doses of 1 and 0,5mg/kg/d. At 1mg/kg/d, it normalizes PAAT and reduces vascular hyperreactivity with no effect on the alteration of the response to acetylcholine induced by hyperoxia. It decreases cardiac and vascular remodeling at all concentrations tested but has no effect on alveolization and vascular density. Finally, it decreases also calcium hyperreactivity of fetal pulmonary VSMCs exposed to hyperoxia. Conclusion: celastrol has a preventive effect on HTP but not on DBP itself. However, mechanisms involved remain unknown.
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Master Thesis
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Submitted on : Friday, January 18, 2019 - 4:15:00 PM
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Claire-Marie Pilard. Hypertension pulmonaire associée à la dysplasie broncho-pulmonaire du nouveau-né prématuré : état actuel des connaissances et étude de l’intérêt du célastrol. Médecine humaine et pathologie. 2018. ⟨dumas-01986269⟩

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