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Ref-1 protects against FeCl3-induced thrombosis and tissue factor expression via the GSK3β–NF-κB pathway
Ref-1 protects against FeCl3-induced thrombosis and tissue factor expression via the GSK3β–NF-κB pathway
- Source :
- The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
- Publication Year :
- 2021
- Publisher :
- The Korean Physiological Society and The Korean Society of Pharmacology, 2021.
-
Abstract
- Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref-1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.
- Subjects :
- 0301 basic medicine
Pathology
medicine.medical_specialty
Endothelium
Physiology
medicine.disease_cause
03 medical and health sciences
Tissue factor
0302 clinical medicine
medicine
Artery occlusion
Thrombus
Pharmacology
Carotid artery thrombosis
business.industry
Carotid Artery Thrombosis
medicine.disease
Thrombosis
030104 developmental biology
medicine.anatomical_structure
APE/Ref-1
Original Article
business
030217 neurology & neurosurgery
Oxidative stress
Artery
Subjects
Details
- Language :
- English
- ISSN :
- 20933827 and 12264512
- Volume :
- 25
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
- Accession number :
- edsair.doi.dedup.....965f9edcb15d24d16602ec73cc37bf40