Albumin–endothelial cell interface

The albumin–endothelial cell interface is a specialized physiological site on the vascular endothelium that regulates the transport and homeostasis of serum albumin. This interface is primarily mediated by two key proteins: the 60-kDa glycoprotein receptor (gp60, also known as albondin) and the neonatal Fc receptor (FcRn) (Schnitzer et al., 1994; Chaudhury et al., 2003). Binding of albumin to gp60 on the luminal surface of endothelial cells triggers a signaling cascade involving Src kinase, which initiates the formation of caveolae for the transcytosis of albumin across the endothelial barrier (Tiruppathi et al., 1997). Simultaneously, FcRn within the endothelial endosomes binds albumin to protect it from lysosomal degradation, recycling it back into the bloodstream and thereby maintaining high plasma concentrations (Sand et al., 2014). This interface is a major therapeutic target for drug delivery systems, particularly nanoparticle albumin-bound (nab) technology. Drugs like nab-paclitaxel exploit the gp60-mediated transcytosis pathway to achieve enhanced accumulation in tumor tissues, which often exhibit increased albumin demand and overexpression of albumin-binding proteins like SPARC (Desai et al., 2006). Additionally, many long-acting peptide and protein drugs are designed to bind albumin or incorporate an Fc-fusion to leverage the FcRn-mediated recycling at this interface. Dysregulation of the albumin–endothelial cell interface is implicated in various pathological states, including inflammatory edema and cancer.

Other names

Endothelial albumin transport systemgp60-mediated transcytosis pathwayAlbondin-mediated transportAlbumin-endothelial barrier

Drugs targeting this interface utilize caveolae-mediated transcytosis via gp60 binding for tissue penetration and neonatal Fc receptor (FcRn) binding for recycling and half-life extension.