CONICET | Buscador de Institutos y Recursos Humanos

Cardiovascular diseases are increasing at alarming rates in both developed and developing countries. Although lifestyle choices and genetic predisposition are main contributors to cardiometabolic diseases, growing evidence indicates that in utero exposure to adverse environmental conditions leads the developing offspring to have numerous risk factors, which may have an impact later in life.Maternal diabetes is a prevalent pathology that increases the risk of cardiovascular diseases in the offspring. The heart is one of the main target organs affected by this metabolic disease from the embryonic stage and until the adult life. Putative mechanism involved in intrauterine programming of heart damage evidenced in experimental models of maternal diabetes will be presented. The focus will be on altered pathways that regulates cardiac cellular metabolism, the damaging effects of the prooxidant and proinflammatory environment and alterations on the cardiac extracellular matrix remodeling. The role of three main players of these pathways will be discussed: mechanistic target of rapamycin, a cellular sensor for energy metabolism and nutrient availability that controls cellular growth and metabolism, peroxisome proliferator activated receptors, nuclear receptors highly involved in heart metabolic processes and lipid metabolism and the transcription factor forkhead box protein O1 which participates in myocardial metabolic stress adaptation, oxidative stress, endothelial dysfunction and other processes related to inflammation and apoptosis.All these pathways are interconnected evidencing the complexity of this process but also bringing opportunities to facilitate intervention to provide protective effects to prevent the programming of cardiovascular diseases in the offspring of diabetic pregnancies.