CTSS Modulates Stress-Related Carotid Artery Thrombosis in a Mouse FeCl 3 Model.

Autor: Xu S; 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.; 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., Piao L; 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.; 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., Wan Y; 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.; 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., Huang Z; Department of Neurology, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan (Z.H.)., Meng X; Department of Vascular Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China (X.M.)., Inoue A; Community Healthcare & Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan (A.I., M.K.).; Institute of Innovation for Future Society, Nagoya University, Aichi-ken, Japan (A.I., M.K.)., Wang H; 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.; 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., Yue X; 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.; 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., Jin X; 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.; 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., Shi GP; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (G.-P.S.)., Kuzuya M; Community Healthcare & Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan (A.I., M.K.).; Institute of Innovation for Future Society, Nagoya University, Aichi-ken, Japan (A.I., M.K.).; Meitetsu Hospital, Nagoya, Japan (M.K.)., Cheng XW; 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.; 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.
Jazyk: angličtina
Zdroj: Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2023 Jul; Vol. 43 (7), pp. e238-e253. Date of Electronic Publication: 2023 Apr 27.
DOI: 10.1161/ATVBAHA.122.318455
Abstrakt: Background: 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.
Methods: Six-week-old wild-type mice (CTSS +/+ ) and CTSS-deficient mice (CTSS -/- ) randomly assigned to nonstress and 2-week immobilization stress groups underwent iron chloride3 (FeCl 3 )-induced carotid thrombosis surgery for morphological and biochemical studies.
Results: On day 14 poststress/surgery, stress had increased the lengths and weights of thrombi in the CTSS +/+ 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 +/+ mice, the stressed CTSS -/- mice had decreased levels of PAI-1, vWF, TNF (tumor necrosis factor)-α, interleukin-1β, toll-like receptor-4, cleaved-caspase 3, cytochrome c , p16 INK4A , gp91 phox , p22 phox , 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-GSK3α/β (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-induced apoptosis of human umbilical vein endothelial cells, and they altered apoptosis-related proteins.
Conclusions: CTSS inhibition appeared to improve the stress-related thrombosis in mice that underwent FeCl 3 -induction surgery, possibly by reducing vascular inflammation, oxidative stress, and apoptosis. CTSS could thus become a candidate therapeutic target for chronic psychological stress-related thrombotic events in metabolic cardiovascular disease.
Competing Interests: Disclosures None.
Databáze: MEDLINE
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