Connexins in endothelial barrier function - novel therapeutic targets countering vascular hyperpermeability
- PMID: 27488046
- DOI: 10.1160/TH16-03-0210
Connexins in endothelial barrier function - novel therapeutic targets countering vascular hyperpermeability
Abstract
Prolonged vascular hyperpermeability is a common feature of many diseases. Vascular hyperpermeability is typically associated with changes in the expression patterns of adherens and tight junction proteins. Here, we focus on the less-appreciated contribution of gap junction proteins (connexins) to basal vascular permeability and endothelial dysfunction. First, we assess the association of connexins with endothelial barrier integrity by introducing tools used in connexin biology and relating the findings to customary readouts in vascular biology. Second, we explore potential mechanistic ties between connexins and junction regulation. Third, we review the role of connexins in microvascular organisation and development, focusing on interactions of the endothelium with mural cells and tissue-specific perivascular cells. Last, we see how connexins contribute to the interactions between the endothelium and components of the immune system, by using neutrophils as an example. Mounting evidence of crosstalk between connexins and other junction proteins suggests that we rethink the way in which different junction components contribute to endothelial barrier function. Given the multiple points of connexin-mediated communication arising from the endothelium, there is great potential for synergism between connexin-targeted inhibitors and existing immune-targeted therapeutics. As more drugs targeting connexins progress through clinical trials, it is hoped that some might prove effective at countering vascular hyperpermeability.
Keywords: Connexins; endothelial cells; gap junctions; permeability.
Similar articles
-
Function of Connexins in the Interaction between Glial and Vascular Cells in the Central Nervous System and Related Neurological Diseases.Neural Plast. 2018 Jun 10;2018:6323901. doi: 10.1155/2018/6323901. eCollection 2018. Neural Plast. 2018. PMID: 29983707 Free PMC article. Review.
-
Continuous blood purification ameliorates endothelial hyperpermeability in SAP patients with MODS by regulating tight junction proteins via ROCK.Int J Artif Organs. 2013 Oct;36(10):700-9. doi: 10.5301/ijao.5000216. Epub 2013 Aug 2. Int J Artif Organs. 2013. PMID: 23918271
-
Microvascular endothelial cell hyperpermeability induced by endogenous caspase 3 activator staurosporine.J Trauma Acute Care Surg. 2013 Feb;74(2):516-23. doi: 10.1097/TA.0b013e31827a0620. J Trauma Acute Care Surg. 2013. PMID: 23354245
-
Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells.J Cell Physiol. 2006 Jul;208(1):123-32. doi: 10.1002/jcp.20647. J Cell Physiol. 2006. PMID: 16547974
-
Targets for pharmacological intervention of endothelial hyperpermeability and barrier function.Vascul Pharmacol. 2002 Nov;39(4-5):257-72. doi: 10.1016/s1537-1891(03)00014-4. Vascul Pharmacol. 2002. PMID: 12747965 Review.
Cited by
-
Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.Int J Mol Sci. 2022 Jun 30;23(13):7303. doi: 10.3390/ijms23137303. Int J Mol Sci. 2022. PMID: 35806312 Free PMC article. Review.
-
Connexins may play a critical role in cigarette smoke-induced pulmonary hypertension.Arch Toxicol. 2022 Jun;96(6):1609-1621. doi: 10.1007/s00204-022-03274-6. Epub 2022 Mar 27. Arch Toxicol. 2022. PMID: 35344070 Review.
-
The Cx43 Carboxyl-Terminal Mimetic Peptide αCT1 Protects Endothelial Barrier Function in a ZO1 Binding-Competent Manner.Biomolecules. 2021 Aug 12;11(8):1192. doi: 10.3390/biom11081192. Biomolecules. 2021. PMID: 34439858 Free PMC article.
-
Changes in connexin 43 in inflammatory skin disorders: Eczema, psoriasis, and Steven-Johnson syndrome/toxic epidermal necrolysis.Health Sci Rep. 2021 Feb 19;4(1):e247. doi: 10.1002/hsr2.247. eCollection 2021 Mar. Health Sci Rep. 2021. PMID: 33659713 Free PMC article.
-
The Role of Connexin 43 in Lung Disease.Life (Basel). 2020 Dec 19;10(12):363. doi: 10.3390/life10120363. Life (Basel). 2020. PMID: 33352732 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous