Early modulation of macrophage ROS-PPARγ-NF-κB signalling by sonodynamic therapy attenuates neointimal hyperplasia in rabbits.
Jianting YaoXuezhu ZhaoFancheng TanXiaoru CaoShuyuan GuoXiang LiZhen HuangKamal DiabakteLu WangMingyu LiuZhaoqian ShenBicheng LiZhengyu CaoSiqi ShengMinqiao LuYang CaoHong JinZhiguo ZhangYe TianPublished in: Scientific reports (2020)
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.
Keyphrases
- smooth muscle
- oxidative stress
- adipose tissue
- signaling pathway
- cell death
- dna damage
- endoplasmic reticulum stress
- diabetic rats
- single cell
- rheumatoid arthritis
- lps induced
- type diabetes
- magnetic resonance imaging
- nuclear factor
- cell therapy
- photodynamic therapy
- fatty acid
- physical activity
- atrial fibrillation
- mesenchymal stem cells
- skeletal muscle
- immune response
- drug induced
- bone marrow
- risk assessment
- human health
- wound healing
- electronic health record