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High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia.

ABSTRACT: Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman's correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.

SUBMITTER: Bai G

PROVIDER: S-EPMC8125627 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Following acute myocardial infarction, clinical studies show alterations in the blood levels of corin, a cardiac-selective activator of the natriuretic peptides pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). However, the temporal changes in circulating and cardiac corin levels and their relationships to the severity of myocardial infarction have not been studied. The main objective of this study was to examine the relationship between cardiac and circulating corin levels and their association with cardiac systolic function and infarct size during the early phase of acute myocardial infarction (<72 h) in a translationally relevant induced coronary ligation mouse model. This acute phase timeline was chosen to correlate with the clinical practice within which blood samples are collected from myocardial infarction patients. Heart and plasma samples were examined at 3, 24, and 72 hours post acute myocardial infarction. Plasma corin levels were examined by enzyme-linked immunosorbent assay, transcripts of cardiac corin, pro-ANP and pro-BNP by quantitative real-time polymerase chain reaction, cardiac corin expression by immunohistology, infarct size by histology and heart function by echocardiography. Plasma corin levels were significantly increased at 3 (P<0.05), 24 (P<0.001), and 72 hours (P<0.01) post-acute myocardial infarction. In contrast, cardiac corin transcript levels dropped by 5% (P>0.05), 69% (P<0.001) and 65% (P<0.001) and immunoreactive cardiac corin protein levels dropped by 30% (P<0.05), 76% (P<0.001) and 75% (P<0.001), while cardiac pro-ANP and pro-BNP transcript levels showed an opposite pattern. Plasma corin levels were negatively correlated with immunoreactive cardiac corin (P<0.01), ejection fraction (P<0.05) and fractional shortening (P<0.05), but positively correlated with infarct size (P<0.01). In conclusion, acute myocardial infarction induces rapid increases in plasma corin and decreases in cardiac corin levels. In the early phase of acute myocardial infarction, plasma corin levels are inversely correlated with heart function and may reflect the severity of myocardial damage.

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High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia.

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