Vascular Permeability: Regulation Pathways and Role in Kidney Diseases

Abstract

Background: Vascular permeability (VP) is a fundamental aspect of vascular biology. A growing number of studies have revealed that many signalling pathways govern VP in both physiological and pathophysiological conditions. Furthermore, emerging evidence identifies VP alteration as a pivotal pathogenic factor in acute kidney injury, chronic kidney disease, diabetic kidney disease, and other proteinuric diseases. Therefore, perceiving the connections between these pathways and the aetiology of kidney disease is an important task as such knowledge may trigger the development of novel therapeutic or preventive medical approaches. In this regard, the discussion summarizing VP-regulating pathways and associating them with kidney diseases is highly warranted.

Summary: Major pathways of VP regulation comprise angiogenic factors including vascular endothelial growth factor/VEGFR, angiopoietin/Tie, and class 3 semaphorin/neuropilin and inflammatory factors including histamine, platelet-activating factor, and leukocyte extravasation. These pathways mainly act on vascular endothelial cadherin to modulate adherens junctions of endothelial cells (ECs), thereby augmenting VP via the paracellular pathway. Elevated VP in diverse kidney diseases involves EC apoptosis, imbalanced regulatory factors, and many other pathophysiological events, which in turn exacerbates renal structural and functional disorders. Measures improving VP effectively ameliorate the diseased kidney in terms of tissue injury, endothelial dysfunction, kidney function, and long-term prognosis. Key Messages: (1) Angiogenic factors, inflammatory factors, and adhesion molecules represent major pathways that regulate VP. (2) Vascular hyperpermeability links various pathophysiological processes and plays detrimental roles in multiple kidney diseases.

Keywords: Acute kidney injury; Chronic kidney disease; Diabetic kidney disease; Vascular endothelial cadherin; Vascular permeability.