Impaired activity of adherens junctions contributes to endothelial dilator dysfunction in ageing rat arteries

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12438-list-0001">Ageing‐induced endothelial dysfunction contributes to organ dysfunction and progression of cardiovascular disease. VE‐cadherin clustering at adherens junctions promotes protective endothelial functions, including endothelium‐dependent dilatation.Ageing increased internalization and degradation of VE‐cadherin, resulting in impaired activity of adherens junctions.Inhibition of VE‐cadherin clustering at adherens junctions (function‐blocking antibody; FBA) reduced endothelial dilatation in young arteries but did not affect the already impaired dilatation in old arteries. After junctional disruption with the FBA, dilatation was similar in young and old arteries.Src tyrosine kinase activity and tyrosine phosphorylation of VE‐cadherin were increased in old arteries. Src inhibition increased VE‐cadherin at adherens junctions and increased endothelial dilatation in old, but not young, arteries. Src inhibition did not increase dilatation in old arteries treated with the VE‐cadherin FBA.Ageing impairs the activity of adherens junctions, which contributes to endothelial dilator dysfunction. Restoring the activity of adherens junctions could be of therapeutic benefit in vascular ageing.