Deep Vein Thrombosis is Modulated by Inflammation Regulated via Sirtuin 1/NF-κB Signalling Pathway in a Rat Model

Abstract

Background Inflammation plays an important role in thrombus formation, and Sirtuin 1 (SIRT1) negatively regulates inflammation via deacetylating nuclear factor-kappa B. However, the relationship between SIRT1-regulated inflammation and deep vein thrombosis (DVT) is still unknown. Objective The aim of this study was to investigate whether SIRT1 plays a critical role in inferior vena cava (IVC) stenosis-induced DVT. Materials and Methods Thrombus weight and histopathologic analysis of IVC were evaluated at different time points after IVC stenosis in rats. Serum levels of inflammatory cytokines and protein expressions of SIRT1, acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF) in thrombosed IVC were assessed. Besides, the effects of resveratrol (RES, a SIRT1 agonist) and EX527 (a selective SIRT1 inhibitor) on DVT were evaluated. Results Thrombus weight was increased from 1 to 3 days after IVC stenosis, and then was decreased afterwards. Leukocytes infiltration appeared and serum levels of cytokines were significantly increased in rats of IVC stenosis. SIRT1 protein expression was significantly down-regulated at 1 hour and 1 day after stenosis, while p-p65, Ace-p65 and TF protein expressions appeared a contrary trend. RES reduced thrombus weight, leukocytes infiltration, levels of tumour necrosis factor-α and interleukin-1β and protein expressions of Ace-p65 and TF as well. Moreover, RES significantly increased the protein and messenger ribonucleic acid expressions of SIRT1, while EX527 abolished the protective effects of RES. Conclusion SIRT1 activation attenuated IVC stenosis-induced DVT via anti-inflammation in rats. Therefore, SIRT1 may be a potential therapeutic target that could ameliorate DVT.

Biochemical mechanism and biological effects of the inhibition of silent information regulator 1 (SIRT1) by EX-527 (SEN0014196 or selisistat)

“…For example, mice and rats suffering from ischaemia, sepsis, or chronic obstructive pulmonary disease were treated with several natural products including melatonin 76,[87][88][89] , diallyl trisulphide 90 , and punicalagin 86 . Other examples include the effects of ghrelin 82,84 , hydrogen-rich saline 83 , carbon monoxide 62 , the SIRT1 activators resveratrol 67,79,91 and scopolin 92 , and the PARP inhibitor 3aminobenzamide 36 . In all these cases, EX-527 was used as a pharmacological tool to demonstrate that SIRT1 activation was involved in the beneficial effects of the compounds under study.…”

Aqueous Extract of Whitmania Pigra Whitman Alleviates Thrombus Burden Via Sirtuin 1/NF-κB Pathway

“…EX527 was administered once and was given 20 min before surgery. 26,32 The rats in the normal, sham, and model groups were orally administered with distilled water.…”

“…25 Our previous study has shown that DVT is associated with inflammation via SIRT1/NF-kB signaling pathway. 26 Whitmania pigra Whitman (W pigra) is a traditional Chinese medicine (TCM). It was first recorded in Shen Nong's Herbal Classic (Shen Nong Ben Cao Jing) about 2400 y ago and is included in Chinese Pharmacopoeia 2015 edition.…”

Data for DHK effect on thrombus weight, blood coagulation, blood cell counts and whole blood viscosity in deep vein thrombosis rats

“…IVC thrombus was induced as described previously [2]. In brief, rats were anesthetized with intraperitoneal injection of 36 mg/kg pentobarbital sodium and then a 2-cm incision was performed along the abdominal midline.…”