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http://dx.doi.org/10.4196/kjpp.2021.25.1.59

Ref-1 protects against FeCl3-induced thrombosis and tissue factor expression via the GSK3β-NF-κB pathway  

Lee, Ikjun (Department of Physiology and Medical Science, Chungnam National University School of Medicine)
Nagar, Harsha (Department of Physiology and Medical Science, Chungnam National University School of Medicine)
Kim, Seonhee (Department of Physiology and Medical Science, Chungnam National University School of Medicine)
Choi, Su-jeong (Department of Physiology and Medical Science, Chungnam National University School of Medicine)
Piao, Shuyu (Department of Physiology and Medical Science, Chungnam National University School of Medicine)
Ahn, Moonsang (Department of Surgery, Chungnam National University School of Medicine)
Jeon, Byeong Hwa (Department of Physiology and Medical Science, Chungnam National University School of Medicine)
Oh, Sang-Ha (Department of Plastic and Reconstructive Surgery, Chungnam National University School of Medicine)
Kang, Shin Kwang (Department of Thoracic and Cardiovascular Surgery, Chungnam National University Hospital, Chungnam National University School of Medicine)
Kim, Cuk-Seong (Department of Physiology and Medical Science, Chungnam National University School of Medicine)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.25, no.1, 2021 , pp. 59-68 More about this Journal
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. Ref1 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.
Keywords
APE/Ref-1; Carotid artery thrombosis; Endothelium; Tissue factor;
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