Targeting Rho kinase to restore endothelial barrier function following vascular scaffold implantation |
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| Affiliation: | 1. Department of Biotechnology, Savitribai Phule Pune University, Ganeshkhind Road, Pune 411007, India;1. S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande CEP 79.117-900, Brazil;2. Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília 70790-160, Brazil;1. Amity Institute of Click Chemistry Research and Studies, Amity University Uttar Pradesh, Noida 201313, India;2. Amity Institute of Nanotechnology, Amity University Uttar Pradesh, Noida 201313, India;1. Institute of Pharmacology and Toxicology, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;2. Pediatric Cancer Research Center, National Clinical Research Center for Child Health, Hangzhou, Zhejiang 310052, China;3. Cancer Center, Zhejiang University, Hangzhou 310058, China;4. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China |
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| Abstract: | Vascular scaffold implantation induces injury to the intimal layer and causes discontinuity of the regenerated endothelial monolayer, compromising barrier integrity, increasing permeability, and allowing the transmigration of leukocytes and lipoproteins into the subendothelial space. Mechanical vascular wall stretching triggers Ras homolog family member A (RhoA)/Rho kinase-mediated actomyosin contractility and destabilization of adherens junctions, leading to endothelial barrier dysfunction. Assembly of intercellular adhesion and actin cytoskeletal organization of interendothelial junctions are controlled by downregulation of RhoA guanosine triphosphatase (GTPase)-mediated barrier-disruptive activity and upregulation of repressor-activator protein 1 (Rap1) and Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase-mediated cytoskeletal reorganization, leading to endothelial barrier stabilization. This review highlights the involvement of Rho GTPases in the disruption of endothelial barrier integrity following vascular scaffold implantation and the targeting of downstream Rho-associated protein kinases, which signal the network to restore endothelial barrier integrity and stability. |
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| Keywords: | endothelial barrier integrity permeability vascular scaffold Rho kinase in-stent neoatherosclerosis Ang" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" angiopoietin cRGD" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" cyclic Arg-Gly-Asp peptide GTPases" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" guanosine triphosphatases HMG-CoA" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" 3-hydroxy-3-methylglutaryl-coenzyme A PECAM-1" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" platelet endothelial cell adhesion molecule-1 ROCK" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" Rho-associated protein kinase S1P" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" sphingosine-1-phosphate VE-cadherin" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" vascular endothelial-cadherin VEGFR-2" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" vascular endothelial growth factor receptor-2 |
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