ERK5/KLF2 activation is involved in the reducing effects of puerarin on monocyte adhesion to endothelial cells and atherosclerotic lesion in apolipoprotein E-deficient mice

Publication date: August 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 8Author(s): Yan Deng, Tingwen Lei, Hongmei Li, Xiaochuan Mo, Zhuting Wang, Hailong OuAbstractPuerarin has properties of anti-oxidation and anti-inflammation, which has been demonstrated protective effects in atherosclerosis and other cardiovascular diseases. However, the detail molecular mechanism still remains unclear. Here, we determined whether the atheroprotective effect of puerarin was by reducing monocyte adhesion and explored the underlying mechanism. The results showed that puerarin dose- and time-dependently reduced oxLDL-induced monocyte THP-1 adhesion to HUVECs and the expression of adhesion-related genes such as VCAM-1, ICAM-1, MCP-1 and IL-8 in HUVECs. Puerarin activated ERK5 phosphorylation and up-regulated expressions of downstream KLF2 and its targeted genes endothelial nitric oxide synthase and thrombomodulin. However, the protective effects were reversed by ERK5/KLF2 pathway inhibitor XDM8-92, BIX02189 or KLF2 siRNA suggesting the pathway involved in the function. The ex vivo assay, in which THP-1 adhesion to endothelium isolated from apoE−/− mice received various treatments further confirmed the results from HUVECs. Finally, we found that the atherosclerotic lesions in both cross sections at aortic root and whole aorta were significantly reduced in high fat-diet (HFD) mice with puerarin treatment compared with the HFD-only mice, but ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research