{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:39:30Z","timestamp":1792093170242,"version":"4.4.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Exposure to chronic psychological stress is a risk factor for metabolic cardiovascular disease. Given the important role of lysosomal CTSS (cathepsin S) in human pathobiology, we examined the role of CTSS in stress-related thrombosis, focusing on inflammation, oxidative stress, and apoptosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Six-week-old wild-type mice (CTSS\n              <jats:sup>\n                <jats:italic toggle=\"yes\">+\/+<\/jats:italic>\n              <\/jats:sup>\n              ) and CTSS-deficient mice (CTSS\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ) randomly assigned to nonstress and 2-week immobilization stress groups underwent iron chloride3 (FeCl\n              <jats:sub>3<\/jats:sub>\n              )-induced carotid thrombosis surgery for morphological and biochemical studies.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              On day 14 poststress\/surgery, stress had increased the lengths and weights of thrombi in the CTSS\n              <jats:sup>\n                <jats:italic toggle=\"yes\">+\/+<\/jats:italic>\n              <\/jats:sup>\n              mice, plus harmful changes in the levels of PAI-1 (plasminogen activation inhibitor-1), ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 13 motifs), and vWF (von Willebrand factor) and arterial tissue CTSS expression. Compared to the nonstressed CTSS\n              <jats:sup>\n                <jats:italic toggle=\"yes\">+\/+<\/jats:italic>\n              <\/jats:sup>\n              mice, the stressed CTSS\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice had decreased levels of PAI-1, vWF, TNF (tumor necrosis factor)-\u03b1, interleukin-1\u03b2, toll-like receptor-4, cleaved-caspase 3, cytochrome\n              <jats:italic toggle=\"yes\">c<\/jats:italic>\n              , p16\n              <jats:sup>INK4A<\/jats:sup>\n              , gp91\n              <jats:sup>phox<\/jats:sup>\n              , p22\n              <jats:sup>phox<\/jats:sup>\n              , ICAM-1 (intercellular adhesion molecule-1), MCP-1 (monocyte chemoattractant protein-1), MyD88 (myeloid differentiation primary response 88), and MMP (matrix metalloproteinase)-2\/-9 and increased levels of ADAMTS13, SOD (superoxide dismutase)-1\/-2, eNOS (endothelial NO synthase), p-Akt (phospho-protein kinase B), Bcl-2 (B-cell lymphoma-2), p-GSK3\u03b1\/\u03b2 (phospho-glycogen synthase kinases alpha and beta), and p-Erk1\/2 (phospho-extracellular signal-regulated kinase 1 and 2) mRNAs and\/or proteins. CTSS deletion also reduced the arterial thrombus area and endothelial loss. A pharmacological inhibition of CTSS exerted a vasculoprotective action. In vitro, CTSS silencing and overexpression, respectively, reduced and increased the stressed serum and oxidative stress\u2013induced apoptosis of human umbilical vein endothelial cells, and they altered apoptosis-related proteins.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              CTSS inhibition appeared to improve the stress-related thrombosis in mice that underwent FeCl\n              <jats:sub>3<\/jats:sub>\n              -induction surgery, possibly by reducing vascular inflammation, oxidative stress, and apoptosis. CTSS could thus become a candidate therapeutic target for chronic psychological stress\u2013related thrombotic events in metabolic cardiovascular disease.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.122.318455","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T05:02:00Z","timestamp":1682571720000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["CTSS Modulates Stress-Related Carotid Artery Thrombosis in a Mouse FeCl\n            <sub>3<\/sub>\n            Model"],"prefix":"10.1161","volume":"43","author":[{"given":"Shengnan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Cardiology and Hypertension (S.X., L.P., Y.W., H.W., X.Y., X.J., X.W.C.), Yanbian University Hospital, Yanji, China."},{"name":"Jilin Provincial Key Laboratory of Stress and Cardiovascular Disease (S.X., L.P., Y.W., H.W., X.Y., X.J., X.W.C.), Yanbian University Hospital, Yanji, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5808-9990","authenticated-orcid":true,"given":"Limei","family":"Piao","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Hypertension (S.X., L.P., Y.W., H.W., X.Y., X.J., X.W.C.), Yanbian University Hospital, Yanji, China."},{"name":"Jilin Provincial Key Laboratory of Stress and Cardiovascular Disease (S.X., L.P., Y.W., H.W., X.Y., X.J., X.W.C.), Yanbian University Hospital, Yanji, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Hypertension (S.X., L.P., Y.W., H.W., X.Y., X.J., X.W.C.), Yanbian University Hospital, Yanji, China."},{"name":"Jilin Provincial Key Laboratory of Stress and Cardiovascular Disease (S.X., L.P., Y.W., H.W., X.Y., X.J., X.W.C.), Yanbian University Hospital, Yanji, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan (Z.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7666-2508","authenticated-orcid":true,"given":"Xiangkun","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China (X.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiko","family":"Inoue","sequence":"additional","affiliation":[{"name":"Community Healthcare &amp; 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