Mucopolysaccharidosis type II (MPSII, also called Hunter disease) is a rare, X-linked recessive disorder characterized by iduronate-2-sulfatase (IDS) deficiency and storage of the lysosomal undegraded glycosaminoglycans (GAGs) dermatan sulfate (DS) and heparan sulfate (HS). [1]. The pathogenic variants described in MPSII can result in severe or attenuated phenotypes of disease [2]. MPSII is characterized as a multisystemic disorder with accumulation of HS and DS in most tissues and organs. It causes several abnormalities, including neurocognitive decline, skeletal abnormalities, and cardiovascular disease. Among the most common cardiovascular alterations found in humans are valvular abnormalities, left ventricular hypertrophy, and hypertension [3]. Accumulation of GAGs progressively occurs in the ventricular muscle, artery aortic lumen and cardiac valves, mainly mitral and aortic ones. Progressive left ventricular hypertrophy and interventricular septal thickening can lead to loss cardiac function, affecting the life expectancy of patients and causing their premature death [4]. Histological abnormalities that are observed in the aortic artery wall include accumulation of GAGs, thickening, and disruption of elastin fibers. The result of these histological alterations may lead to constriction or dilation of large vessels, as the aortic artery, with aortic root dilatation (ARD) being frequently observed in MPSII patients [5]. The animal model develops most of disease features which suggests that the knockout mice (Ids-KO) may develop cardiac abnormalities as well [6].

Different approaches have been used to treat MPSII, including enzyme replacement therapy (ERT), considered the standard of care. However, treated patients still present some cardiovascular alterations, in particular the aortic and valvular abnormalities [7,8]. In the context, animal models are important tools to assess the progressive alterations of the disease. In previous studies using another MPS mouse model (Mucopolysaccharidosis type I - MPSI), the decline of cardiac function could be observed only at six months of age, despite GAGs storage in the myocardium being visualized in histological sections as early as 2-month-old [9]. In other study we showed the involvement of proteases overexpression as one of the alterations that can lead to loss of cardiac function, as consequence of GAGs accumulation in MPSI mice [10]. Since the two disorders are very similar, we hypothesized that a somewhat similar process could happen in MPSII. Studies in the mouse model suggest that the treatment with recombinant enzyme often have limited impact on the cardiovascular aspect of the disease, corroborating the patient data's [4,11]. Garcia and colleagues conducted a study on the murine model of MPSII, showing results on the outcome of the disease, in several organs, but despite of showing histologic accumulation of GAGs in heart tissue, the study did not present data on the loss of cardiac function [6]. Thus, the aim of this study was to perform a temporal assessment of cardiovascular function in Ids-KO animals and to look for possible mechanisms involved in the evolution of the disease.