TY - JOUR
T1 - Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease
AU - Aman, Jurjan
AU - Margadant, Coert
N1 - Funding Information: Work in our laboratories is supported by the Landsteiner Foundation for Blood Transfusion Research (CM; grant no. 2019), NWO ZonMW (JA; VENI grant no. 09150161910155), and the Dutch Lung Fund (JA; grant no. 11.1.20.025). Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/2/3
Y1 - 2023/2/3
N2 - The endothelium is a dynamic, semipermeable layer lining all blood vessels, regulating blood vessel formation and barrier function. Proper composition and function of the endothelial barrier are required for fluid homeostasis, and clinical conditions characterized by barrier disruption are associated with severe morbidity and high mortality rates. Endothelial barrier properties are regulated by cell-cell junctions and intracellular signaling pathways governing the cytoskeleton, but recent insights indicate an increasingly important role for integrin-mediated cell-matrix adhesion and signaling in endothelial barrier regulation. Here, we discuss diseases characterized by endothelial barrier disruption, and provide an overview of the composition of endothelial cell-matrix adhesion complexes and associated signaling pathways, their crosstalk with cell-cell junctions, and with other receptors. We further present recent insights into the role of cell-matrix adhesions in the developing and mature/adult endothelium of various vascular beds, and discuss how the dynamic regulation and turnover of cell-matrix adhesions regulates endothelial barrier function in (patho)physiological conditions like angiogenesis, inflammation and in response to hemodynamic stress. Finally, as clinical conditions associated with vascular leak still lack direct treatment, we focus on how understanding of endothelial cell-matrix adhesion may provide novel targets for treatment, and discuss current translational challenges and future perspectives.
AB - The endothelium is a dynamic, semipermeable layer lining all blood vessels, regulating blood vessel formation and barrier function. Proper composition and function of the endothelial barrier are required for fluid homeostasis, and clinical conditions characterized by barrier disruption are associated with severe morbidity and high mortality rates. Endothelial barrier properties are regulated by cell-cell junctions and intracellular signaling pathways governing the cytoskeleton, but recent insights indicate an increasingly important role for integrin-mediated cell-matrix adhesion and signaling in endothelial barrier regulation. Here, we discuss diseases characterized by endothelial barrier disruption, and provide an overview of the composition of endothelial cell-matrix adhesion complexes and associated signaling pathways, their crosstalk with cell-cell junctions, and with other receptors. We further present recent insights into the role of cell-matrix adhesions in the developing and mature/adult endothelium of various vascular beds, and discuss how the dynamic regulation and turnover of cell-matrix adhesions regulates endothelial barrier function in (patho)physiological conditions like angiogenesis, inflammation and in response to hemodynamic stress. Finally, as clinical conditions associated with vascular leak still lack direct treatment, we focus on how understanding of endothelial cell-matrix adhesion may provide novel targets for treatment, and discuss current translational challenges and future perspectives.
KW - angiogenesis
KW - cell-matrix adhesions
KW - edema
KW - endothelium
KW - inflammation
KW - integrins
UR - http://www.scopus.com/inward/record.url?scp=85147270880&partnerID=8YFLogxK
U2 - https://doi.org/10.1161/CIRCRESAHA.122.322332
DO - https://doi.org/10.1161/CIRCRESAHA.122.322332
M3 - Review article
C2 - 36730379
SN - 0009-7330
VL - 132
SP - 355
EP - 378
JO - Circulation Research
JF - Circulation Research
IS - 3
ER -