PMID- 37128920
OWN - NLM
STAT- MEDLINE
DCOM- 20230623
LR  - 20230627
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 43
IP  - 7
DP  - 2023 Jul
TI  - CTSS Modulates Stress-Related Carotid Artery Thrombosis in a Mouse FeCl(3) Model.
PG  - e238-e253
LID - 10.1161/ATVBAHA.122.318455 [doi]
AB  - 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)-alpha, interleukin-1beta, 
      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-GSK3alpha/beta 
      (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.
FAU - Xu, Shengnan
AU  - Xu S
AD  - 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.
AD  - 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.
FAU - Piao, Limei
AU  - Piao L
AUID- ORCID: 0000-0001-5808-9990
AD  - 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.
AD  - 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.
FAU - Wan, Ying
AU  - Wan Y
AD  - 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.
AD  - 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.
FAU - Huang, Zhe
AU  - Huang Z
AD  - Department of Neurology, University of Occupational and Environmental Health, 
      Kitakyushu, Fukuoka, Japan (Z.H.).
FAU - Meng, Xiangkun
AU  - Meng X
AUID- ORCID: 0000-0002-7666-2508
AD  - Department of Vascular Surgery, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China (X.M.).
FAU - Inoue, Aiko
AU  - Inoue A
AD  - Community Healthcare & Geriatrics, Nagoya University Graduate School of Medicine, 
      Nagoya, Japan (A.I., M.K.).
AD  - Institute of Innovation for Future Society, Nagoya University, Aichi-ken, Japan 
      (A.I., M.K.).
FAU - Wang, Hailong
AU  - Wang H
AD  - 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.
AD  - 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.
FAU - Yue, Xueling
AU  - Yue X
AD  - 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.
AD  - 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.
FAU - Jin, Xianglan
AU  - Jin X
AD  - 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.
AD  - 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.
FAU - Shi, Guo-Ping
AU  - Shi GP
AUID- ORCID: 0000-0001-5809-2567
AD  - Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA (G.-P.S.).
FAU - Kuzuya, Masafumi
AU  - Kuzuya M
AD  - Community Healthcare & Geriatrics, Nagoya University Graduate School of Medicine, 
      Nagoya, Japan (A.I., M.K.).
AD  - Institute of Innovation for Future Society, Nagoya University, Aichi-ken, Japan 
      (A.I., M.K.).
AD  - Meitetsu Hospital, Nagoya, Japan (M.K.).
FAU - Cheng, Xian Wu
AU  - Cheng XW
AUID- ORCID: 0000-0002-9758-0632
AD  - 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.
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230427
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - U38V3ZVV3V (ferric chloride)
RN  - EC 3.4.22.27 (cathepsin S)
RN  - 0 (von Willebrand Factor)
RN  - 0 (Plasminogen Activator Inhibitor 1)
SB  - IM
MH  - Mice
MH  - Humans
MH  - Animals
MH  - *Carotid Artery Thrombosis
MH  - von Willebrand Factor/metabolism
MH  - *Cardiovascular Diseases
MH  - Plasminogen Activator Inhibitor 1/genetics
MH  - *Thrombosis/etiology/metabolism
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - Inflammation/pathology
OTO - NOTNLM
OT  - apoptosis
OT  - cathepsin
OT  - endothelial cell
OT  - oxidative stress
OT  - thrombosis
COIS- Disclosures None.
EDAT- 2023/05/02 06:42
MHDA- 2023/06/23 06:42
CRDT- 2023/05/02 05:26
PHST- 2023/06/23 06:42 [medline]
PHST- 2023/05/02 06:42 [pubmed]
PHST- 2023/05/02 05:26 [entrez]
AID - 10.1161/ATVBAHA.122.318455 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2023 Jul;43(7):e238-e253. doi: 
      10.1161/ATVBAHA.122.318455. Epub 2023 Apr 27.