Detoxification and activating blood circulation decoction reduces restenosis involving the TLR4/NF-κB pathway after balloon injury

Prostaglandins Other Lipid Mediat. 2019 Feb:140:1-8. doi: 10.1016/j.prostaglandins.2018.11.002. Epub 2018 Nov 16.

Abstract

Restenosis is a major problem after percutaneous coronary intervention (PCI) treatment. Inflammation is one of the major core mechanisms involved in the occurrence of restenosis, and plays an important role in intimal hyperplasia. Detoxification and activating blood circulation decoction (DABCD) is a traditional Chinese medicine that is used in the treatment and prevention of atherosclerotic and inflammatory diseases. Our previous studies demonstrated that DABCD-mediated cardioprotection involves anti-inflammatory mechanisms and could be developed as a novel drug for the treatment of vascular smooth muscle cell (VSMC) proliferation and aortic restenosis. A rat model of postoperative restenosis after PCI was generated by balloon injury to determine the protective effects and potential mechanisms of DABCD. The injured segments of aortae were collected on days 14 and 28 after the operation to observe the morphological changes in the vascular structure and measure the proportion of inflammatory factors in plasma and vascular tissues, as well as test the proliferative activity of VSMCs. The expression of related proteins, namely, Toll-like receptor (TLR) 4 and nuclear factor (NF)-κB, in the mechanistic study was clarified by western blot analysis. We tested the hypothesis that the cardioprotective effects of DABCD on aortic restenosis are associated with the inhibition of aortic intimal hyperplasia in this model. Our results showed that DABCD has protective effect on rat aortic restenosis and the anti-inflammatory mechanism of DABCD on balloon-induced restenosis in rat may be due to its ability to inhibit TLR4-mediated NF-κB signaling pathways. DABCD may be a potential therapeutic agent against restenosis.

Keywords: Detoxification and activating blood circulation decoction; Inflammatory reaction; PCI operation; Restenosis; TLR4/NF-κB; VSMCs proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Balloon Occlusion / adverse effects*
  • Blood Circulation / drug effects*
  • Cell Proliferation / drug effects
  • Coronary Restenosis / etiology
  • Coronary Restenosis / metabolism
  • Coronary Restenosis / pathology
  • Coronary Restenosis / physiopathology*
  • Cytokines / metabolism
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Gene Expression Regulation / drug effects
  • Male
  • Muscle, Smooth, Vascular / pathology
  • NF-kappa B / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Cytokines
  • Drugs, Chinese Herbal
  • NF-kappa B
  • Toll-Like Receptor 4