Amelioration of salvianolic acid C on aortic structure in apolipoprotein E-deficient mice treated with angiotension II.
OBJECTIVE
Aortic aneurysm is a disastrous vascular disease with high morbidity and mortality. Matrix metalloproteinases (MMPs), especially MMP-9, is implicated in the development of aortic aneurysm, but the effective MMP inhibitors are far from development. To develop new candidate compound for aortic aneurysm therapy, we evaluated the effects of salvianolic acid C (SalC) against the formation of aortic aneurysm.


METHODS
Aortic aneurysm was induced by implantation of angiotension II (AngII) minipump in apolipoprotein E-deficient (ApoE-/-) mice. MMPs activity was evaluated by enzyme kinetic analysis in vitro and in-gel gelatin zymography in vivo. The formation of aortic aneurysm was confirmed based on aortic maximum diameter. Hematoxylin and eosin stain was used to evaluate aortic structure, picrosirius red stain was for collagen deposition, and orcein stain was for elastin fragmentation. Macrophage infiltration was detected by CD68 immunohistochemistry.


RESULTS
Firstly, SalC showed significant inhibition on the activity of MMP-2 and MMP-9. Aortic aneurysm was defined as >50% increase in maximum diameter of aorta, and the down-regulated tendency of 20mg/kg SalC against formation of aortic aneurysm was detected. Also, 22.2% rupture was detected in ApoE-/-mice, while no rupture of aortic aneurysm was found with 20mg/kg SalC treatment. Then, SalC was detected to maintain the integrity of aortic structure and protect elastin against fragmentation. Finally, SalC considerably inhibited infiltration of macrophage in the injury site of aorta.


CONCLUSIONS
SalC significantly ameliorated the progression of aortic aneurysm in ApoE-/-mice, and held great potential for aortic aneurysm therapy.
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang 110016, China.
Peng
P
Wu
Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang 110016, China.
Na
N
Han
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Haitao
H
Yu
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Linlin
L
Wang
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Xue
X
Li
Departments of Vascular Surgery, Zhongshan Hospital, Fudan University, China.
Zhihui
Z
Dong
Departments of Vascular Surgery, Zhongshan Hospital, Fudan University, China.
Weiguo
W
Fu
Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, Japan.
Hoichi
H
Yorinaka
Takarazuka University of Medical and Health Care, Hanayashiki-Midorigaoka, Takarazuka City 6660162, Japan.
Kenka
K
Cho
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Wanying
W
Wu
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Xuan
X
Liu
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Min
M
Yang
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
De-An
DA
Guo
Shenyang Pharmaceutical University, Wenhua Road #103, Shenyang 110016, China. Electronic address: yinjun826@sina.com.
Jun
J
Yin
State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: jiangbh@simm.ac.cn.
Baohong
B
Jiang
D000475:Alkenes / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D001014:Aortic Aneurysm / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D004549:Elastin / Q000032:analysis / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008810:Mice, Inbred C57BL; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use*; D001572:Benzofurans
D000475:Alkenes; D001057:Apolipoproteins E; D004549:Elastin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D059808:Polyphenols; C000597819:salvianolic acid C; D001572:Benzofurans
Aortic aneurysm; Matrix metalloproteinase; Salvianolic acid C