ArticleThe American journal of pathology2011
Ultrastructural analysis reveals cAMP-dependent enhancement of microvascular endothelial barrier functions via Rac1-mediated reorganization of intercellular junctions.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Anthrax ET activates Rac1 and RTK signaling to induce F-actin reorganization and endothelial permeability.iScience · 2025Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
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- The Protein Kinase A Inhibitor KT5720 Prevents Endothelial Dysfunctions Induced by High-Dose Irradiation.International journal of molecular sciences · 2024Article
- Epac-2 ameliorates spontaneous colitis in Il-10Journal of cellular and molecular medicine · 2022Article
- Brefeldin A and kifunensine modulate LPS-induced lung endothelial hyperpermeability in human and bovine cells.American journal of physiology. Cell physiology · 2021Article
- Direct Current Stimulation Disrupts Endothelial Glycocalyx and Tight Junctions of the Blood-Brain BarrierFrontiers in cell and developmental biology · 2021Article
- Article
- Cardiomyocyte adhesion and hyperadhesion differentially require ERK1/2 and plakoglobin.JCI insight · 2020Article
- Prolonged activation of cAMP signaling leads to endothelial barrier disruption via transcriptional repression of RRAS.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Increased microvascular permeability in mice lacking Epac1 (Rapgef3).Acta physiologica (Oxford, England) · 2017Article
- Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility.Scientific reports · 2016Article
- Inhibition of endothelial nitric oxide synthase decreases breast cancer cell MDA-MB-231 adhesion to intact microvessels under physiological flows.American journal of physiology. Heart and circulatory physiology · 2016Article
- Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions.Small GTPases · 2016Article
- Reinforcing endothelial junctions prevents microvessel permeability increase and tumor cell adhesion in microvessels in vivo.Scientific reports · 2015Article
- Impedance analysis of GPCR-mediated changes in endothelial barrier function: overview and fundamental considerations for stable and reproducible measurements.Pflugers Archiv : European journal of physiology · 2015Article
- Article
- Control of vascular permeability by adhesion molecules.Tissue barriers · 2015Article
- PKA compartmentalization via AKAP220 and AKAP12 contributes to endothelial barrier regulation.PloS one · 2014Article
- Tonic regulation of vascular permeability.Acta physiologica (Oxford, England) · 2013Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evidence exists that cAMP stabilizes the endothelial barrier, in part via activation of the small GTPase Rac1. However, despite the high medical relevance of this signaling pathway, the mechanistic effects on intercellular contacts on the ultrastructural level are largely unknown. In microvascular endothelial cell monolayers, in which increased cAMP strengthened barrier properties, similar to intact microvessels in vivo, both forskolin and rolipram (F/R) to increase cAMP and 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphorothioate (O-Me-cAMP) to stimulate exchange protein directly activated by cAMP/Ras proximate-1 (EPac/Rap 1) signaling enhanced transendothelial electrical resistance and induced activation of Rac1. Concurrently, augmented immunofluorescence intensity and linearization of signals at cell borders were observed for intercellular junction proteins VE-cadherin and claudin 5. Ultrastructural analysis of the intercellular contact zone architecture documented that exposure to F/R or O-Me-cAMP led to a significant increase in the proportion of contact sites displaying complex interdigitations of cell borders, in which membranes of neighboring cells were closely apposed over comparatively long distances; in addition, they were stabilized by numerous intercellular junctions. Interference with Rac1 activation by NSC-23766 completely abolished both barrier stabilization and contact zone reorganization in response to O-Me-cAMP, whereas F/R-mediated Rac1 activation and barrier enhancement were not affected by NSC-23766. In parallel experiments using macrovascular endothelium, increased cAMP failed to induce Rac1 activation, barrier enhancement, and contact zone reorganization. These results indicate that, in microvascular endothelium, Rac1-mediated alterations in contact zone architecture contribute to cAMP-induced barrier stabilization.
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