Journal
LIFE SCIENCES
Volume 216, Issue -, Pages 140-146Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2018.11.036
Keywords
Genistein; C-reactive protein; Matrix metalloproteinase 9; Angiotensin II; Vascular smooth muscle cells; Atherosclerosis; Inflammation
Funding
- Social Development Grant of Shaanxi Province, China [2012K15-02-04]
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Aims: C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9 are involved in the inflammation of atherosclerosis lesions. Genistein (Gen) has been demonstrated to exert beneficial effect on the cardiovascular system. However, it remains unclear whether Gen produces anti-inflammatory effect in vascular smooth muscle cells (VSMCs). Therefore, we investigated the effects of Gen on CRP and MMP-9 expressions induced by angiotensin (Ang) II in VSMCs and the related molecular mechanism. Main methods: Rat VSMCs were cultured, and Ang II was used as a stimulant for CRP and MMP-9 expressions. CRP level was measured by ELISA. The mRNA and protein expressions of related indexes were identified by reverse transcription-polymerase chain reaction and western blot, respectively. Key findings: Gen inhibited Ang II-stimulated CRP and MMP-9 mRNA and protein expressions in concentrationand time-dependent manners. Additionally, Gen ameliorated Ang II-induced p-ERK1/2, p-p38 and NF-kappa B expressions, antagonized Ang II-downregulated peroxisome proliferation-activated receptor (PPAR) gamma and estrogen receptor (ER) beta-expressions. After treating the VSMCs with GW9662 or ICI182780 in Gen treated groups, inhibitory effect of Gen on CRP and MMP-9 expressions were antagonized in Ang II-stimulated VSMCs. The treatment of VSMCs with ICI182780 abolished downregulations of p-p38/p-ERK1/2, and antagonized upregulation of PPAR. by Gen in Ang II-stimulated VSMCs. Moreover, the inhibitory effect of Gen on Ang II-stimulated NF-kappa B expression was abolished after preincubation of VSMCs with GW9662 in Gen treated groups. Significance: Gen exerts anti-inflammatory property via the ER-p38/ERK1/2-PPAR gamma-NF-kappa B-CRP/MMP-9 signal pathway in Ang II-stimulated VSMCs.
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