Changes in NOS and ARG1 in AMN-SARS-CoV-2
Growing evidence suggests the roles of NOS and ARG1 in immune response
modulation via arginine catabolism and the urea cycle[19, 20]. It
has been shown that ARG1 activity is increased in COVID-19 patients and
correlated with disease severity[21]. Consistently, our study
revealed significantly increased ARG1 mRNA expression in the
AMN-SARS-CoV-2 group (Figure 3A). It is well-established that elevated
ARG1 competes with NOS for arginine, resulting in decreased NOS
activity. Three distinct isoforms of NOS, neuronal NOS (nNOS), inducible
NOS (iNOS), and endothelial NOS (eNOS), regulate vascular health, with
eNOS contributing to healthy blood flow by releasing nitric oxide, which
effectively counteracts arterial tone[22]. Consequently, eNOS levels
were significantly elevated in the AMN-SARS-CoV-2 group (Figure 3A).
UHPLC-LC/MS analysis also identified the upregulation of ADMA (Figure
3B), a known endogenous NOS inhibitor. Increased ADMA could further
contribute to NOS suppression. ROC analysis for ARG1, NOS, and ADMA
yielded AUC values of 0.8571, 0.6837, and 0.7959, respectively (Figure
3C). Correlation analysis indicated that NOS was negatively correlated
with ARG1 (r = -0.428) and ADMA (-0.469). However, NOS displayed no
significant correlation with the metabolites ornithine, citrulline, and
L-proline.