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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

Authors :
Byeong Hwa Jeon
Sang-Ha Oh
Su-jeong Choi
Shin Kwang Kang
Seonhee Kim
Ikjun Lee
Cuk-Seong Kim
Moonsang Ahn
Harsha Nagar
Shuyu Piao
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.

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