Traditional Chinese medication Tongxinluo inhibits inflammatory angiogenesis via Bmx/NF- B/MAPK pathways

The aim of this article is to examine the effect of the traditional Chinese medication Tongxinluo (TXL) on atherosclerotic plaque angiogenesis and stabilization and to explore the mechanism involved. Apolipoprotein E-deficient (apoE−/−) mice were fed a high-fat diet for 20 weeks, and then divided into four groups for 16 weeks' treatment: control (equal volume of buffer) and low-, medium-, and high-dose TXL (0.38, 0.75, and 1.5 g/kg/day, respectively). Vasa vasorum (VV) were identified by perfusion of biotinylated Lycopersicon esculentum (Tomato) lectin. The cellular effect of TXL on tumour necrosis factor α (TNF-α)-stimulated angiogenesis was explored in human umbilical vein endothelial cells. Histology revealed that VV neovascularization was dose-dependently reduced by TXL treatment. Plaque area was smaller with TXL than control treatment and levels of inflammatory cytokines, matrix metalloproteinase 2, and vascular endothelial growth factor A were deceased in TXL-treated mice. Tongxinluo significantly inhibited TNF-α-induced endothelial cell migration, tube formation, and monocyte adhesion in vitro. The mechanism mediating the therapeutic effects of TXL involved inhibited activation of bone marrow kinase in chromosome X (Bmx) and nuclear factor kappa B (NF-κB) and down-regulated phosphorylation of the mitogen-activated protein kinase (MAPK) family members c-Jun N-terminal kinase and p38, but not extracellular signal-regulated kinase 1/2. Tongxinluo inhibits VV proliferation and atherosclerosis progression, thus stabilizing plaque in apoE−/− mice. The anti-angiogenic effects of TXL on atherosclerosis might be attributed to inhibiting inflammatory angiogenesis via Bmx/NF-κB/MAPK pathways.