Early modulation of macrophage ROS-PPARγ-NF-κB signalling by sonodynamic therapy attenuates neointimal hyperplasia in rabbits.

Autor: Yao, Jianting, Zhao, Xuezhu, Tan, Fancheng, Cao, Xiaoru, Guo, Shuyuan, Li, Xiang, Huang, Zhen, Diabakte, Kamal, Wang, Lu, Liu, Mingyu, Shen, Zhaoqian, Li, Bicheng, Cao, Zhengyu, Sheng, Siqi, Lu, Minqiao, Cao, Yang, Jin, Hong, Zhang, Zhiguo, Tian, Ye
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Zdroj: Scientific Reports; 7/15/2020, Vol. 10 Issue 1, p1-14, 14p
Abstrakt: Disruption of re-endothelialization and haemodynamic balance remains a critical side effect of drug-eluting stents (DES) for preventing intimal hyperplasia. Previously, we found that 5-aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) suppressed macrophage-mediated inflammation in atherosclerotic plaques. However, the effects on intimal hyperplasia and re-endothelialization remain unknown. In this study, 56 rabbits were randomly assigned to control, ultrasound, ALA and ALA-SDT groups, and each group was divided into two subgroups (n = 7) on day 3 after right femoral artery balloon denudation combined with a hypercholesterolemic diet. Histopathological analysis revealed that ALA-SDT enhanced macrophage apoptosis and ameliorated inflammation from day 1. ALA-SDT inhibited neointima formation without affecting re-endothelialization, increased blood perfusion, decreased the content of macrophages, proliferating smooth muscle cells (SMCs) and collagen but increased elastin by day 28. In vitro, ALA-SDT induced macrophage apoptosis and reduced TNF-α, IL-6 and IL-1β via the ROS-PPARγ-NF-κB signalling pathway, which indirectly inhibited human umbilical artery smooth muscle cell (HUASMC) proliferation, migration and IL-6 production. ALA-SDT effectively inhibits intimal hyperplasia without affecting re-endothelialization. Hence, its clinical application combined with bare-metal stent (BMS) implantation presents a potential strategy to decrease bleeding risk caused by prolonged dual-antiplatelet regimen after DES deployment. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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