The glomerular endothelium: new insights on function and structure

Abstract

Purpose of review: It is our aim to review the latest findings on the intricate functional and structural properties of the glomerular endothelium. Previously, all focus has been on the podocyte and the glomerular basement membrane (GBM), but it is now clear that the endothelium plays an important part of the glomerular barrier.

Recent findings: We start by giving an overview of recent findings on the glomerular 'endothelial surface layer' (ESL). The ESL has a membrane-bound component, the 'glycocalyx', and a more loosely attached 'cell coat' bound by charge-charge interactions. Damage to the ESL causes proteinuria even if the GBM and the podocytes are intact. Such damage can be caused by, for example, enzymatic digestion of the ESL by increased oxidative stress, or secondary to pathological conditions such as high glucose concentration. Indeed, several studies suggest the ESL to be targeted in diabetes. The correlation is likely to be causal, but the experimental evidence is still indirect. Also, there have been new findings on vascular endothelial growth factor, as well as studies on angiopoietin and angiopoietin-like proteins demonstrating a key role of the endothelium in glomerular disease.

Summary: More conclusive endothelium-specific, inducible transgenic mouse models are still lacking. There are studies, however, showing that the glomerular cell components interact much more intensely than previously recognized. Thus, the glomerular barrier seems to maintain its highly selective properties by an orchestra of intercellular signaling between mesangial, endothelial and epithelial cells. The result resembles a fine-tuned symphony of which we have heard only small parts, and understood even less.