NYMC Faculty Publications
Permissive Role of Vascular Endothelium in Fibrosis: Focus on the Kidney
Author Type(s)
Faculty
DOI
10.1152/ajpcell.00526.2023
Journal Title
American Journal of Physiology. Cell Physiology
First Page
C712
Last Page
C723
Document Type
Article
Publication Date
3-1-2024
Department
Medicine
Abstract
Fibrosis, the morphologic end-result of a plethora of chronic conditions and the scorch for organ function, has been thoroughly investigated. One aspect of its development and progression, namely the permissive role of vascular endothelium, has been overshadowed by studies into (myo)fibroblasts and TGF-β; thus, it is the subject of the present review. It has been established that tensile forces of the extracellular matrix acting on cells are a prerequisite for mechanochemical coupling, leading to liberation of TGF-β and formation of myofibroblasts. Increased tensile forces are prompted by elevated vascular permeability in response to diverse stressors, resulting in the exudation of fibronectin, fibrinogen/fibrin, and other proteins, all stiffening the extracellular matrix. These processes lead to the development of endothelial cells dysfunction, endothelial-to-mesenchymal transition, premature senescence of endothelial cells, perturbation of blood flow, and gradual obliteration of microvasculature, leaving behind "string" vessels. The resulting microvascular rarefaction is not only a constant companion of fibrosis but also an adjunct mechanism of its progression. The deepening knowledge of the above chain of pathogenetic events involving endothelial cells, namely increased permeability-stiffening of the matrix-endothelial dysfunction-microvascular rarefaction-tissue fibrosis, may provide a roadmap for therapeutic interventions deemed to curtail and reverse fibrosis.
Recommended Citation
Goligorsky, M. S. (2024). Permissive Role of Vascular Endothelium in Fibrosis: Focus on the Kidney. American Journal of Physiology. Cell Physiology, 326 (3), C712-C723. https://doi.org/10.1152/ajpcell.00526.2023