Back to Search
Start Over
Catestatin prevents endothelial inflammation and promotes thrombus resolution in acute pulmonary embolism in mice
Catestatin prevents endothelial inflammation and promotes thrombus resolution in acute pulmonary embolism in mice
- Source :
- Bioscience Reports
- Publication Year :
- 2019
- Publisher :
- Portland Press Ltd., 2019.
-
Abstract
- Catestatin (CTS), a catecholamine-release inhibitory peptide, exerts pleiotropic cardiac protective effects. Pulmonary embolism caused by deep vein thrombosis involving vascular dysfunction. The present study aims to investigate the effects of CTS on thrombus formation that may inhibit the development of pulmonary embolism and its potential pathway. Acute pulmonary embolism (APE) model was developed as an in vivo model. The effects of CTS on mice with APE were examined. Human pulmonary artery endothelial cells (HPAECs) were pretreated with CTS before thrombin stimulation, and endothelial inflammation and underlying mechanisms were evaluated in vitro. That plasma CTS level was decreased in APE mice, while the number of platelets was significantly increased. The decreased circulating CTS level negatively associated with the number of platelets. CTS administration increased the survival rate of APE mice and protected against microvascular thrombosis in lung. APE-induced the increase in platelets number and plasma von Willebrand factor (VWF) were inhibited by CTS. Platelets from CTS-treated APE mice showed impaired agonist-induced platelets aggregation and spreading. CTS also ameliorated APE-induced the systemic inflammatory response. In in vivo study, thrombin-induced the increase in inflammation, TLR-4 expression and p38 phosphorylation were abrogated by CTS in HPAECs. Furthermore, TLR-4 overexpression inhibited the effect of CTS on VWF release and inflammation in HPAECs. Collectively, CTS increases thrombus resolution by attenuating endothelial inflammation at partially via inhibiting TLR-4-p38 pathway. The present study may provide a novel approach for anti-thrombosis.
- Subjects :
- 0301 basic medicine
Immunology & Inflammation
Platelet Aggregation
030204 cardiovascular system & hematology
Pharmacology
Biochemistry
Mice
0302 clinical medicine
Platelet
Cells, Cultured
Research Articles
biology
Pharmacology & Toxicology
TLR-4
catestatin
Thrombosis
medicine.anatomical_structure
medicine.symptom
medicine.drug
Blood Platelets
Biophysics
p38
Inflammation
03 medical and health sciences
Thrombin
Von Willebrand factor
medicine.artery
von Willebrand Factor
Chemical Biology
medicine
Animals
Humans
Thrombus
Molecular Biology
thrombus formation
Lung
business.industry
Endothelial Cells
Cell Biology
medicine.disease
Peptide Fragments
Signaling
nervous system diseases
Mice, Inbred C57BL
030104 developmental biology
Cardiovascular System & Vascular Biology
Pulmonary artery
biology.protein
Chromogranin A
Pulmonary Embolism
business
Subjects
Details
- ISSN :
- 15734935 and 01448463
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Bioscience Reports
- Accession number :
- edsair.doi.dedup.....a44b6d4303df6647b096f88f45cc091c
- Full Text :
- https://doi.org/10.1042/bsr20192236