Human pulmonary artery endothelial cells in the model of mucopolysaccharidosis {VI} present a prohypertensive phenotype

摘要

AbstractBackground Mucopolysaccharidosis type {VI} (MPS VI) is an autosomal recessive lysosomal disorder caused by a deficient activity of N-acetylgalactosamine-4-sulfatase (ARSB). Pulmonary hypertension (PH) occurs in {MPS} {VI} patients and is a marker of bad prognosis. Malfunction of endothelium, which regulates vascular tonus and stimulates angiogenesis, can contribute to the occurrence of {PH} in {MPS} VI. Aim The aim of the study was to establish a human {MPS} {VI} cellular model of pulmonary artery endothelial cells (HPAECs) and evaluate how it affects factors that may trigger {PH} such as proliferation, apoptosis, expression of endothelial nitric oxide synthase (eNOS), natriuretic peptide type C (NPPC), and vascular endothelial growth factor A (VEGFA). Results Increasing concentrations of dermatan sulfate (DS) reduce the viability of the cells in both {ARSB} deficiency and controls, but hardly influence apoptosis. The expression of eNOS in {HPAECs} is reduced up to two thirds in the presence of DS. {NPPC} shows a biphasic expression reaction with an increase at 50?μg/mL {DS} and reduction at 0 and 100?μg/mL DS. The expression of {VEGFA} decreases with increasing {DS} concentrations and absence of elastin, and increases with increasing {DS} in the presence of elastin. Conclusion Our data suggest that {MPS} {VI} endothelium presents a prohypertensive phenotype due to the reduction of endothelium's proliferation ability and expression of vasorelaxing factors.