Yiqi-Huoxue Granule (YQHX) Downregulates Prothrombotic Factors by Modulating KLF2 and NF-κB in HUVECs following LPS Stimulation.

Hong Wu,Liping Dai,Dake Qi,Zhen Lei,Haixia Gao,Haibin Tong,Yongjun Han,Xinzhou Wang,Shuibo Gao,Lihua Han,Zhentao Wang

doi:10.1155/2019/9425183

Abstract

The Yiqi-Huoxue granule (YQHX) is a traditional Chinese medication widely used in the therapy of the traditional Chinese medicine diagnosis “Qi deficiency” or “blood stasis” in China. Both these symptoms are related to inflammation, but the mechanisms of YQHX against inflammation are largely unknown. Thus, our present study investigated the effects of YQHX on regulating inflammatory responses induced by lipopolysaccharides (LPS) in HUVECs. Our data found that YQHX remarkably inhibits the production of prothrombotic factors, plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF), while it upregulates the protein expression of Kruppel-like factor 2 (KLF2). The increase in PAI-1 and TF was significantly attenuated through a transgenic knockdown in KLF2 with a Lenti-shKLF2 vector. YQHX also decreases the phosphorylation of nuclear factor-κB (NF-κB) p65 and IκB following LPS stimulation, and it effectively suppresses PAI-1 and TF via a NF-κB-dependent mechanism. Taken together, our results suggest that YQHX provides a notable antithrombotic activity via regulating the KLF2 expression and NF-κB signaling pathway in HUVECs. The KLF2 and NF-κB may be potential therapeutic targets for interventions of inflammation associated with atherosclerosis.

Highlights

Acute ischemic heart disease is a leading cause of death and disability worldwide [1]
We examined if the production of prothrombotic factors plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) could function as a downstream readout to test the potential therapeutic effects of Yiqi-Huoxue granule (YQHX) against cardiovascular diseases
We observed that treatment with pyrrolidine dithiocarbamate (PDTC) significantly reduced the expression of PAI-1 and TF, and PDTC partially attenuates the effects of YQHX on PAI-1 and TF (Figure 6)

Summary

Introduction

Acute ischemic heart disease is a leading cause of death and disability worldwide [1] It is usually associated with luminal thrombosis resulting from vulnerable atherosclerotic erosion or plaque rupture initiated by endothelial dysfunction [2]. The Yiqi-Huoxue granule (YQHX) is a traditional Chinese medication widely used in the therapy of the traditional Chinese medicine diagnosis “Qi deficiency” or “blood stasis” in China. It is composed of Ginseng Radix et Rhizoma The Paeoniae Rubra Radix, Carthami Flos, and Ginseng Radix et Rhizoma extracts have been recognized to produce antithrombotic effects [7,8,9].

Methods

Results

Discussion

Conclusion