Endothelial Dysfunction in Renal Interstitial Fibrosis

Abstract

Kidney disease affects millions of people worldwide and it is now widely accepted that many pathological processes may persist after acute kidney injury that can cause the progression to CKD. Tubulointerstitial fibrosis manifests soon after injury and while many cellular and molecular components of kidney fibrosis have been discovered, largely in animal models, new therapeutic strategies are still desperately needed. The renal endothelium has emerged as important in progression of fibrosis through regulation of hypoxia, inflammation and cellular crosstalk. This review aims to highlight our current understanding of the role of the endothelium in interstitial fibrosis and to identify potential therapeutic targets. © 2016 S. Karger AG, Basel.

Figure 1

Potential targets to prevent endothelial dysfunction and renal interstitial fibrosis. During progressive kidney fibrosis peritubular capillaries recruit inflammatory cells, have increased vascular permeability and vasoconstriction, and undergo rarefaction. Endothelial dysfunction may also lead to pericyte detachment, proliferation, migration and transformation to myofibroblasts. Strategies to enhance endothelial function by promoting survival or angiogenesis (VEGF121), preserving mitochondrial function (SS31), preventing leukocyte adhesion molecule expression and enhancing vascular barrier function (S1P1, IGF1R) may reduce fibrosis.