Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity

Abstract

IMPORTANCE:Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.

A nomogram based on the expression level of angiopoietin-like 4 to predict the severity of community-acquired pneumonia

“…However, our cross-sectional study lacked dynamic changes in ANGPTL4 and cannot yet causally correlate it with sCAP. Nonetheless, on the basis of previous researches [ 14 , 26 , 27 , 39 – 41 ], our study showed that ANGPTL4 was also able to identify sCAP well by constructing a multivariate logistic regression analysis, breaking the ice for subsequent studies.…”

“…The cANGPTL4 induces endothelial cell disruption and compromises the vascular integrity by interacting with integrin α5β1, VE-cadherin, and claudin-5, which may further stimulate intracellular pathways that promote wound and tumorigenesis [ 39 ]. In recent years, several studies have confirmed the role of ANGPTL4 in lung tissue integrity [ 14 , 27 , 39 – 41 ].…”

“…It was reported that ANGPTL4 upregulation was not limited to specific strain of influenza virus [ 27 ]. By comparing samples from coronavirus disease 2019 (COVID-19) patients and healthy individuals, Bhatraju PK et al found that ANGPTL4 expression level in plasma was positively correlated with worse mortality, and ANGPTL4 was increasingly expressed in pulmonary epithelial cells and fibroblasts [ 41 ]. In addition to the infection by influenza and COVID-19 viruses, Li et al demonstrated that immunoneutralization of cANGPTL4 could reduce pulmonary damage in secondary bacteria-infected mice [ 40 ].…”

“…Moreover, several studies have shown that immunoneutralization of ANGPTL4 could significantly reduce vascular leakage and tissue integrity disruption and promote lung recovery [ 14 , 27 , 40 , 41 ], which not only emphasizes the potential of ANGPTL4 as a marker for assessment of pneumonia severity, but also induces a promising therapy, targeting ANGPTL4 for lung recovery.…”

“…Previous studies have shown that different pathogens with different ANGPTL4 protein expression profiles and different ANGPTL4 isoforms are associated with different functions [ 26 , 27 ]. The ELISA method was used to measure the ANGPTL4 expression level in the present study, which has been confirmed to have high affinity for cANGPTL4 with less affinity for full-length and minimal affinity for nANGPTL4 [ 41 ]. Although ELISA is still the first option for detection of ANGPTL4 expression level, it cannot completely separate different ANGPTL4 isoforms [ 30 ].…”