Network Analysis Reveals Proteins Associated with Aortic Dilatation in Mucopolysaccharidoses.

Abstract

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.