AUTHOR=Zhang Rui , Wang Lan , Zhao Qin-Hua , Jiang Rong , Gong Su-Gang , Jiang Xin , Xu Xi-Qi , He Yang-Yang , Li Yuan , Jing Zhi-Cheng 

TITLE=Alteration of Extracellular Superoxide Dismutase in Idiopathic Pulmonary Arterial Hypertension

JOURNAL=Frontiers in Medicine

VOLUME=7

YEAR=2020

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.00509

DOI=10.3389/fmed.2020.00509

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Superoxide dismutases (SODs) are an important family of antioxidant enzymes that modulate reactive oxygen species levels. It is largely unknown which SOD isoform(s) change <italic>in vivo</italic> in idiopathic pulmonary arterial hypertension (IPAH) patients.</p><p><bold>Methods:</bold> A total of 133 consecutive adult IPAH patients who underwent bone morphogenetic protein receptor type 2 (<italic>BMPR2)</italic> genetic counseling were enrolled in this prospective study. The plasma activities of three subtypes of SOD [copper–zinc (Cu/Zn-SOD), manganese (Mn-SOD), and extracellular SOD (Ec-SOD)] were examined.</p><p><bold>Results:</bold> The activities of SODs were significantly lower in IPAH patients than in healthy subjects. However, only Ec-SOD activity in <italic>BMPR2</italic> mutation patients was significantly decreased compared to those in patients without a mutation. The reduced Ec-SOD activity was markedly associated with mean pulmonary arterial pressure, pulmonary vascular resistance (PVR), and 6-min walking distance (6MWD). The reduction of Mn-SOD activity was only associated with 6MWD. There was no association between Cu/Zn-SOD and hemodynamics. Patients with a lower Ec-SOD level had a worse survival compared to those with a higher baseline. The reduced Ec-SOD activity and the raised PVR increased the mortality risk.</p><p><bold>Conclusions:</bold> Ec-SOD was correlated with <italic>BMPR2</italic> mutation, hemodynamic dysfunction, and poor outcomes. Circulating Ec-SOD could be a potentially vital antioxidant enzyme in the pathogenesis of IPAH.</p>