Integrin affinity modulation critically regulates atherogenic endothelial activation in vitro and in vivo.

Autor: Al-Yafeai Z; Departments of Molecular and Cellular Physiology, LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States., Pearson BH; Departments of Molecular and Cellular Physiology, LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States., Peretik JM; Pathology and Translational Pathobiology,LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States., Cockerham ED; Pathology and Translational Pathobiology,LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States., Reeves KA; Pathology and Translational Pathobiology,LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States., Bhattarai U; Departments of Molecular and Cellular Physiology, LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States., Wang D; Pathology and Translational Pathobiology,LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States., Petrich BG; Department of Pediatrics, Shreveport, LA, Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA, United States., Orr AW; Departments of Molecular and Cellular Physiology, LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States.; Cell Biology and Anatomy,LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States.; Pathology and Translational Pathobiology,LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States.; Department of Pathology and Translational Pathobiology, 1501 Kings Hwy, Biomedical Research Institute, Rm. 6-21, LSU Health Sciences Center - Shreveport, Shreveport, LA 71130, United States. Electronic address: aorr@lsuhsc.edu.
Jazyk: angličtina
Zdroj: Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2021 Feb; Vol. 96, pp. 87-103. Date of Electronic Publication: 2020 Nov 04.
DOI: 10.1016/j.matbio.2020.10.006
Abstrakt: While vital to platelet and leukocyte adhesion, the role of integrin affinity modulation in adherent cells remains controversial. In endothelial cells, atheroprone hemodynamics and oxidized lipoproteins drive an increase in the high affinity conformation of α5β1 integrins in endothelial cells in vitro, and α5β1 integrin inhibitors reduce proinflammatory endothelial activation to these stimuli in vitro and in vivo. However, the importance of α5β1 integrin affinity modulation to endothelial phenotype remains unknown. We now show that endothelial cells (talin1 L325R) unable to induce high affinity integrins initially adhere and spread but show significant defects in nascent adhesion formation. In contrast, overall focal adhesion number, area, and composition in stably adherent cells are similar between talin1 wildtype and talin1 L325R endothelial cells. However, talin1 L325R endothelial cells fail to induce high affinity α5β1 integrins, fibronectin deposition, and proinflammatory responses to atheroprone hemodynamics and oxidized lipoproteins. Inducing the high affinity conformation of α5β1 integrins in talin1 L325R endothelial cells suggest that NF-κB activation and maximal fibronectin deposition require both integrin activation and other integrin-independent signaling. In endothelial-specific talin1 L325R mice, atheroprone hemodynamics fail to promote inflammation and macrophage recruitment, demonstrating a vital role for integrin activation in regulating endothelial phenotype.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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