| First Author | Regal-McDonald K | Year | 2020 |
| Journal | PLoS One | Volume | 15 |
| Issue | 3 | Pages | e0230358 |
| PubMed ID | 32208424 | Mgi Jnum | J:286625 |
| Mgi Id | MGI:6403082 | Doi | 10.1371/journal.pone.0230358 |
| Citation | Regal-McDonald K, et al. (2020) Assessment of ICAM-1 N-glycoforms in mouse and human models of endothelial dysfunction. PLoS One 15(3):e0230358 |
| abstractText | Endothelial dysfunction is a critical event in vascular inflammation characterized, in part, by elevated surface expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is heavily N-glycosylated, and like other surface proteins, it is largely presumed that fully processed, complex N-glycoforms are dominant. However, our recent studies suggest that hypoglycosylated or high mannose (HM)-ICAM-1 N-glycoforms are also expressed on the cell surface during endothelial dysfunction, and have higher affinity for monocyte adhesion and regulate outside-in endothelial signaling by different mechanisms. Whether different ICAM-1 N-glycoforms are expressed in vivo during disease is unknown. In this study, using the proximity ligation assay, we assessed the relative formation of high mannose, hybrid and complex alpha-2,6-sialyated N-glycoforms of ICAM-1 in human and mouse models of atherosclerosis, as well as in arteriovenous fistulas (AVF) of patients on hemodialysis. Our data demonstrates that ICAM-1 harboring HM or hybrid epitopes as well as ICAM-1 bearing alpha-2,6-sialylated epitopes are present in human and mouse atherosclerotic lesions. Further, HM-ICAM-1 positively associated with increased macrophage burden in lesions as assessed by CD68 staining, whereas alpha-2,6-sialylated ICAM-1 did not. Finally, both HM and alpha-2,6-sialylated ICAM-1 N-glycoforms were present in hemodialysis patients who had AVF maturation failure compared to successful AVF maturation. Collectively, these data provide evidence that HM- ICAM-1 N-glycoforms are present in vivo, and at levels similar to complex alpha-2,6-sialylated ICAM-1 underscoring the need to better understand their roles in modulating vascular inflammation. |
