Remodelación cardiovascular inducida por hipoxia intermiente. Reversibilidad y efecto de la edad

Abstract

Obstructive sleep apnea syndrome (OSAS) is a chronic disease prevalent in the adult population and is considered a major public health problem due mainly to its cardiovascular morbidity and mortality. Chronic intermittent hypoxia (CIH) is considered the main deleterious factor involved in the cardiovascular consequences associated with OSAS. The first study was directed to assess the reversibility of CIH-induced cardiovascular remodeling in a murine model of OSAS. The alterations observed at the aortic and cardiac level after exposure to six weeks of CIH were normalized after a period under normoxia conditions, as a translational model of the effective treatment of the disease. Continuing in the same line of research, the effect of age on cardiovascular remodeling induced by IH was studied. The results showed cardiovascular protection in the mice with advanced age, and in young mice a cardiovascular remodeling was observed similar to the natural decline associated with aging. In view of what was observed, the third study was aimed at defining the molecular mechanisms that explain the cardiovascular remodeling induced by CIH observed in the second study and how they are modulated by age. In this study it was found that the regulation of gene expression under CIH exposure is organ-dependent and is modulated by age. The fourth and final study was conducted in patients with OSAS treated with the treatment of choice, continuous positive airway pressure (CPAP). First, the effect of CPAP on clinical and biological variables was evaluated; secondly, it was possible to define a prediction model of treatment response in terms of changes in nocturnal blood pressure. The results suggested the use of ambulatory blood pressure monitoring before CPAP treatment as a key tool in the discrimination of patients who will reduce cardiovascular risk from those patients who will have a detrimental effect when are treated.