Mucopolysaccharidoses are caused by a deficiency of enzymes involved in the degradation of glycosaminoglycans. Heart diseases are a significant cause of morbidity and mortality in MPS patients, even in conditions in which enzyme replacement therapy is available. In this sense, cardiovascular manifestations, such as heart hypertrophy, cardiac function reduction, increased left ventricular chamber, and aortic dilatation, are among the most frequent. However, the downstream events which influence the heart dilatation process are unclear. Here, we employed systems biology tools together with transcriptomic data to investigate new elements that may be involved in aortic dilatation in Mucopolysaccharidoses syndrome. We identified candidate genes involved in biological processes related to inflammatory responses, deposition of collagen, and lipid accumulation in the cardiovascular system that may be involved in aortic dilatation in the Mucopolysaccharidoses I and VII. Furthermore, we investigated the molecular mechanisms of losartan treatment in Mucopolysaccharidoses I mice to underscore how this drug acts to prevent aortic dilation. Our data indicate that the association between the TGF-b signaling pathway, Fos, and Col1a1 proteins can play an essential role in aortic dilation's pathophysiology and its subsequent improvement by losartan treatment.

粘多糖症是由参与糖胺聚糖降解的酶缺乏引起的。心脏病是 MPS 患者发病率和死亡率的重要原因，即使在酶替代疗法可用的情况下也是如此。从这个意义上说，心血管表现，如心脏肥大、心功能降低、左心室腔增加和主动脉扩张，是最常见的。然而，影响心脏扩张过程的下游事件尚不清楚。在这里，我们使用系统生物学工具和转录组数据来研究可能与粘多糖症综合征主动脉扩张有关的新元素。我们确定了与炎症反应、胶原蛋白沉积、心血管系统中的脂质积累可能与粘多糖病 I 和 VII 中的主动脉扩张有关。此外，我们研究了氯沙坦治疗粘多糖 I 小鼠的分子机制，以强调这种药物如何防止主动脉扩张。我们的数据表明，TGF-b 信号通路、Fos 和 Col1a1 蛋白之间的关联可以在主动脉扩张的病理生理学及其随后通过氯沙坦治疗的改善中发挥重要作用。