Abstract
Acute myocardial infarction (AMI) remains the leading cause of mortality in the world.
Early intervention using salvianolic acids (SA) can substantially improve clinical
outcomes. However, in spite of the great achievements that have been made in elucidating
the protective effects of SA on AMI, the effects of SA on the contractile performance
of the left ventricle (LV) and the underlying mechanism are still not so clear. In
the present study, AMI was introduced by ligation of the left anterior descending
coronary artery near the main pulmonary artery. Administration of SA significantly
decreased infarct size, improved LV function and appearance of the myocardium and
decreased myocardial malondialdehyde levels compared with the AMI group. Furthermore,
treatment with SA significantly downregulated the mRNA expression level and activity
of matrix metalloproteinase-9 (MMP-9), but did not regulate the tissue inhibitor of
metalloproteinase-1 (TIMP-1) expression level at the infarct area. Lisinopril (an
angiotensin converting enzyme inhibitor), which holds potential effects on cardioprotection,
was chosen as the positive control in this study. Lisinopril elevated LV function
and appearance of the myocardium, decreased malondialdehyde levels without an influence
on infarct size, and regulated the MMP-9 enzyme level but not the MMP-9 mRNA and TIMP-1
protein levels. These findings suggest that early SA treatment is effective to improve
LV function; and SA may exert preventative effects against myocardial remodeling after
infarction.
Key words
Salvia miltiorrhiza
- Labiatae - salvianolic acids - acute myocardial infarction - matrix metalloproteinase‐9
- cardioprotection
References
1
Judd J T, Wexler B C.
Prolyl hydroxylase and collagen metabolism after experimental myocardial infarction.
Am J Physiol.
1975;
228
212-216
2
Jugdutt B I.
Ventricular remodeling after infarction and the extracellular collagen matrix: when
is enough enough?.
Circulation.
2003;
108
1395-1403
3
Janicki J S, Brower G L, Gardner J D, Chancey A L, Stewart Jr J A.
The dynamic interaction between matrix metalloproteinase activity and adverse myocardial
remodeling.
Heart Fail Rev.
2004;
9
33-42
4
Ahmed S H, Clark L L, Pennington W R, Webb C S, Bonnema D D, Leonardi A H, McClure C D,
Spinale F G, Zile M R.
Matrix metalloproteinases/tissue inhibitors of metalloproteinases relationship between
changes in proteolytic dceterminants of matrix composition and structural, functional,
and clinical manifestations of hypertensive heart disease.
Circulation.
2006;
113
2089-2096
5
Brower G L, Gardner J D, Forman M F, Murray D B, Voloshenyuk T, Levick S P, Janicki J S.
The relationship between myocardial extracellular matrix remodeling and ventricular
function.
Eur J Cardiothorac Surg.
2006;
30
604-610
6
Gallagher G, Menzie S, Huang Y, Jackson C, Hunyor S N.
Regional cardiac dysfunction is associated with specific alterations in inflammatory
cytokines and matrix metalloproteinases after acute myocardial infarction in sheep.
Basic Res Cardiol.
2007;
102
63-72
7
Rohde L E, Aikawa M, Cheng G C, Sukhova G, Solomon S D, Libby P, Pfeffer J, Pfeffer M A,
Lee R T.
Echocardiography-derived left ventricular end-systolic regional wall stress and matrix
remodeling after experimental myocardial infarction.
J Am Coll Cardiol.
1999;
33
835-842
8
Chang P N, Mao J C, Huang S H, Ning L, Wang Z J, On T, Duan W, Zhu Y Z.
Analysis of cardioprotective effects using purified Salvia miltiorrhiza extract on isolated rat hearts.
J Pharmacol Sci.
2006;
101
245-249
9
Shi C S, Huang H C, Wu H L, Kuo C H, Chang B I, Shiao M S, Shi G Y.
Salvianolic acid B modulates hemostasis properties of human umbilical vein endothelial
cells.
Thromb Res.
2007;
119
769-775
10
Zhang H S, Wang S Q.
Salvianolic acid B from Salvia miltiorrhiza inhibits tumor necrosis factor-α(TNF-α)-induced MMP‐2 upregulation in human aortic
smooth muscle cells via suppression of NAD(P)H oxidase-derived reactive oxygen species.
J Mol Cell Cardiol.
2006;
41
138-148
11
Kang E S, Lee G T, Kim B S, Kim C H, Seo G H, Han S J, Hur K Y, Ahn C W, Ha H, Jung M,
Ahn Y S, Cha B S, Lee H C.
Lithospermic acid B ameliorates the development of diabetic nephropathy in OLETF rats.
Eur J Pharmacol.
2008;
579
418-425
12
Lima C F, Valentao P C, Andrade P B, Seabra R M, Fernandes-Ferreira M, Pereira-Wilson C.
Water and methanolic extracts of Salvia officinalis protect HepG2 cells from t-BHP induced oxidative damage.
Chem Biol Interact.
2007;
167
107-115
13
Jiang B, Zhang L, Li M, Wu W, Yang M, Wang J, Guo D A.
Salvianolic acids prevent aculte doxorubicin cardiotoxiciy in mice through suppression
of oxidative stress.
Food Chem Toxicol.
2008;
46
1510-1515
14
Yao Y, Wu W Y, Liu A H, Deng S S, Bi K S, Liu X, Guo D A.
Interaction of salvianolic acids and notoginsengnosides in inhibition of ADP-induced
platelet aggregation.
Am J Chin Med.
2008;
36
313-328
15
Ling S, Dai A, Guo Z, Komesaroff P A.
A preparation of herbal medicine Salvia miltiorrhiza reduces expression of intercellular adhesion molecule-1 and development of atherosclerosis
in apolipoprotein E-deficient mice.
J Cardiovasc Pharmacol.
2008;
51
38-44
16
Liu A H, Guo H, Ye M, Lin Y H, Sun J H, Xu M, Guo D A.
Detection, characterization and identification of phenolic acids in Danshen using
high-performance liquid chromatography with diode array detection and electrospray
ionization mass spectrometry.
J Chromatogr A.
2007;
1161
170-182
17
Yamamoto D, Takai S, Jin D, Inagaki S, Tanaka K, Miyazaki M.
Molecular mechanism of imidapril for cardiovascular protection via inhibition of MMP‐9.
J Mol Cell Cardiol.
2007;
43
670-676
18
Yamamoto D, Takai S, Miyazaki M.
Prediction of interaction mode between a typical ACE inhibitor and MMP‐9 active site.
Biochem Biophys Res Commun.
2007;
354
981-984
19
Jiang B, Hattori N, Liu B, Kitagawa K, Inagaki C.
Expression of swelling-and/or pH-regulated chloride channels (ClC‐2, 3, 4 and 5) in
human leukemic and normal immune cells.
Life Sci.
2002;
70
1383-1394
20
Martin M U, Wesche H.
Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor
family.
Biochim Biophys Acta.
2002;
1592
265-280
21
Spinale F G.
Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac
form and function.
Physiol Rev.
2007;
87
1285-1342
22
Mukherjee R, Mingoia J T, Bruce J A, Austin J S, Stroud R E, Escobar G P, McClister Jr D M,
Allen C M, Alfonso-Jaume M A, Fini M E, Lovett D H, Spinale F G.
Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9
transcription after myocardial infarction.
Am J Physiol Heart Circ Physiol.
2006;
291
H2216-H2228
23
Karim M A, Ferguson A G, Wakim B T, Samarel A M.
In vivo collagen turnover during development of thyroxine-induced left ventricular hypertrophy.
Am J Physiol.
1991;
260
C316-C326
24
Cleutjens J P, Verluyten M J, Smiths J F, Daemen M J.
Collagen remodeling after myocardial infarction in the rat heart.
Am J Pathol.
1995;
147
325-338
25
Tao Z Y, Cavasin M A, Yang F, Liu Y H, Yang X P.
Temporal changes in matrix metalloproteinase expression and inflammatory response
associated with cardiac rupture after myocardial infarction in mice.
Life Sci.
2004;
74
1561-1572
26
Long C S.
The role of interleukin-1 in the failing heart.
Heart Fail Rev.
2001;
6
81-94
27
Wilson E M, Moainie S L, Baskin J M, Lowry A S, Deschamps A, Mukherjee R, Guy T S,
John-Sutton St MG, Gorman 3rd J H.
Region- and type-specific induction of matrix metalloproteinases in post-myocardial
infarction remodeling.
Circulation.
2003;
107
2857-2863
Prof. De-an Guo
Shanghai Zhangjiang Hitech Park
Guoshoujing Road 199
Shanghai 201203
People's Republic of China
Phone: + 86 21 50 80 55 22
Fax: + 86 21 50 27 27 89
Email: gda@bjmu.edu.cn