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Salvianolic acid B attenuates MMP‐2 and MMP‐9 expression in vivo in apolipoprotein‐E‐deficient mouse aorta and in vitro in LPS‐treated human aortic smooth muscle cells
Author(s) -
Lin ShingJong,
Lee ITa,
Chen YungHsiang,
Lin FengYen,
Sheu LiMin,
Ku HungHai,
Shiao MingShi,
Chen JawWen,
Chen YuhLien
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21042
Subject(s) - vascular smooth muscle , downregulation and upregulation , apolipoprotein b , matrix metalloproteinase , zymography , endocrinology , in vivo , medicine , chemistry , inflammation , pharmacology , biology , biochemistry , cholesterol , smooth muscle , microbiology and biotechnology , gene
Salvianolic acid B (Sal B), a water‐soluble antioxidant derived from a Chinese medicinal herb, is believed to have multiple therapeutic and preventive against human vascular diseases, including atherosclerosis and restenosis. To elucidate the underlying cellular mechanisms, we produced hypercholesterolemia by feeding apo‐E‐deficient mice a 0.15% cholesterol diet and inflammation in human aortic smooth muscle cells (HASMCs) with the endotoxin lipopolysaccharide (LPS), focusing on the metallopreteinases MMP‐2 and MMP‐9, the relevant signal transduction pathways and the effects of Sal B. Immunohistochemical analyses indicated apo‐E‐deficient mice fed a 0.15% cholesterol diet for 12 weeks exhibited thickened intima and elevated levels of MMP‐2 and MMP‐9 in aortic sections, both of which were attenuated by 0.3% Sal B dietary supplement. Western blotting and zymography analyses indicated that unstimulated HASMCs exhibited basal levels of protein and activity levels for MMP‐2 and barely detectable levels for MMP‐9, both of which were markedly upregulated by LPS, which also induced cell migration. Sal B significantly attenuated upregulations of both MMPs as well as the LPS‐induced cell migration through the inactivation of MMP‐2 and MMP‐9 protein synthesis as well as the downregulation of the extracellular‐signal‐regulated kinase 1/2 (ERK1/2) and c‐Jun NH 2 ‐terminal kinase (JNK). These results demonstrate that Sal B has anti‐migration properties on smooth muscle cells and may explain its anti‐atherosclerotic properties. This novel mechanism of action of Sal B, in addition to its previously reported inhibition of LDL oxidation, may help explain its efficacy in the treatment of atherosclerosis. J. Cell. Biochem. 100: 372–384, 2007. © 2006 Wiley‐Liss, Inc.