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Cathepsin V, specifically expressed in humans, is involved in vascular diseases through its elastolytic and collagenolytic activities. The aim of this study was to determine the effects of cathepsin V on <jats:sc>l<\/jats:sc>\u2010homocysteine\u2010induced vascular inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>A high methionine diet\u2010induced hyperhomocysteinaemic mouse model was used to assess cathepsin V expression and vascular inflammation. Cultures of HUVECs were challenged with <jats:sc>l<\/jats:sc>\u2010homocysteine and the cathepsin L\/V inhibitor SID to assess the pro\u2010inflammatory effects of cathepsin V. Transfection and antisense techniques were utilized to investigate the effects of cathepsin V on the dual\u2010specificity protein phosphatases (DUSPs) and MAPK pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Cathepsin L (human cathepsin V homologous) was increased in the thoracic aorta endothelial cells of hyperhomocysteinaemic mice; <jats:sc>l<\/jats:sc>\u2010homocysteine promoted cathepsin V expression in HUVECs. SID suppressed the activity of cathepsin V and reversed the up\u2010regulation of inflammatory cytokines (IL\u20106, IL\u20108 and TNF\u2010\u03b1), adhesion and chemotaxis of leukocytes and vascular inflammation induced by <jats:sc>l<\/jats:sc>\u2010homocysteine <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Increased cathepsin V promoted the degradation of DUSP6 and DUSP7, phosphorylation and subsequent nuclear translocation of ERK1\/2, phosphorylation of STAT1 and expression of IL\u20106, IL\u20108 and TNF\u2010\u03b1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>This study has identified a novel mechanism, which shows that <jats:sc>l<\/jats:sc>\u2010homocysteine\u2010induced upregulation of cathepsin V mediates vascular endothelial inflammation under high homocysteine condition partly via ERK<jats:sub>1\/2<\/jats:sub>\/STAT1 pathway. This mechanism could represent a potential therapeutic target in hyperaemia\u2010associated vascular diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.8\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v175.8\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13920","type":"journal-article","created":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T05:08:05Z","timestamp":1497935285000},"page":"1157-1172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["<scp>l<\/scp>\u2010Homocysteine\u2010induced cathepsin V mediates the vascular endothelial inflammation in hyperhomocysteinaemia"],"prefix":"10.1111","volume":"175","author":[{"given":"Yi\u2010Ping","family":"Leng","sequence":"first","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha China"},{"name":"Center for Vascular Disease and Translational 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