Restricted accessResearch articleFirst published online 2012-3
Angiotensin II induces extracellular matrix metalloproteinase inducer expression via an AT1R dependent pathway in aortic atherosclerotic plaque in apolipoprotein E knockout mice
The pathogenesis of acute coronary syndrome is rupture of vulnerable plaque. Extracellular matrix metalloproteinase inducer (EMMPRIN) is reported to have a important role in the destabilization of atheroma. Objectives: this investigation examined the effect of angiotensin II (Ang II) on EMMPRIN expression in atherosclerotic plaques in ApoE knockout mice. Methods: ApoE knockout mice were fed a high fat diet to establish an atherosclerosis model then intervention was made with Ang II and valsartan. EMMPRIN gene and its protein expression were measured by real-time PCR immunohistochemistry, and Western blot. Results: EMMPRIN gene and protein expression intervened with Ang II were significantly increased; valsartan could inhibit the effect of Ang II. Conclusion: Ang II up-regulated EMMPRIN expression in atherosclerotic plaque via AT1R, and valsartan could inhibit the effect of Ang II.
NiculescuFRusH. The role of complement activation in atherosclerosis. Immunol Res2004; 30: 73–80.
2.
YoonYWKwonHMHwangKC. Upstream regulation of matrix metalloproteinase by EMMPRIN; extracellular matrix metalloproteinase inducer in advanced atherosclerotic plaque. Atherosclerosis2005; 180: 37–44.
3.
IaconoKTBrownALGreeneMISaouafSJ. CD147 immunoglobulin superfamily receptor function and role in pathology. Exp Mol Pathol2007; 83: 283–295.
4.
MajorTCLiangLLuXRoseburyWBocanTM. Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced upon monocyte differentiation and is expressed in human atheroma. Arterioscler Thromb Vasc Biol2002; 22: 1200–1207.
5.
SchmidtRBultmannAUngererM. Extracellular matrix metalloproteinase inducer regulates matrix metalloproteinase activity in cardiovascular cells: implications in acute myocardial infarction. Circulation2006; 113: 834–841.
6.
JiangBXuSHouXPimentelDRCohenRA. Angiotensin II differentially regulates interleukin-1-beta-inducible NO synthase (iNOS) and vascular cell adhesion molecule-1 (VCAM-1) expression: role of p38 MAPK. J Biol Chem2004; 279: 20363–20368.
7.
GuoRWYangLXWangHLiuBWangL. Angiotensin II induces matrix metalloproteinase-9 expression via a nuclear factor-kappaB-dependent pathway in vascular smooth muscle cells. Regul Pept2008; 147: 37–44.
8.
BrowatzkiMLarsenDPfeifferCA. Angiotensin II stimulates matrix metalloproteinase secretion in human vascular smooth muscle cells via nuclear factor-kappaB and activator protein 1 in a redox-sensitive mannerJ Vasc Res2005; 42: 415–423.
9.
ChaturvediN. HOPE and extension of the indications for ACE inhibitors? Heart Outcomes Prevention Evaluation. Lancet2000; 355: 246–247.
10.
FoxKM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet2003; 362: 782–788.
11.
SuzukiJIwaiMMogiM. Eplerenone with valsartan effectively reduces atherosclerotic lesion by attenuation of oxidative stress and inflammation. Arterioscler Thromb Vasc Biol2006; 26: 917–921.
12.
JohnsonJLJacksonCL. Atherosclerotic plaque rupture in the apolipoprotein E knockout mouse. Atherosclerosis2001; 154: 399–406.
13.
XuJCarreteroOASheselyEG. The kinin B1 receptor contributes to the cardioprotective effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in mice. Exp Physiol2009; 94: 322–329.
14.
Nakashima APYRainesEWBreslowJLRossR. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb Vasc Biol1994; 14: 133–140.
15.
JohnsonJCarsonKWilliamsH. Plaque rupture after short periods of fat feeding in the apolipoproteine-knockout mouse: model characterization and effects of pravastatin treatment. Circulation2005; 111: 1422–1430.
16.
RosenfeldMEPolinskyPVirmaniRKauserKRubanyiGSchwartzSM. Advanced atherosclerotic lesions in the innominate artery of the ApoE knockout mouse. Arterioscler Thromb Vasc Biol2000; 20: 2587–2592.
17.
WeissDTaylorWR. Deoxycorticosterone acetate salt hypertension in apolipoprotein E−/− mice results in accelerated atherosclerosis: the role of angiotensin II. Hypertension2008; 51: 218–224.
18.
ZhuWKhachiSHaoQ. Upregulation of EMMPRIN after permanent focal cerebral ischemia. Neurochem Int2008; 52: 1086–1091.
19.
SluijterJPPulskensWPSchoneveldAH. Matrix metalloproteinase 2 is associated with stable and matrix metalloproteinases 8 and 9 with vulnerable carotid atherosclerotic lesions: a study in human endarterectomy specimen pointing to a role for different extracellular matrix metalloproteinase inducer glycosylation forms. Stroke2006; 37: 235–239.
20.
DahlofBDevereuxRBKjeldsenSE. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet2002; 359: 995–1003.
21.
MochizukiSDahlofBShimizuM. Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity–mortality study. Lancet2007; 369: 1431–1439.
22.
Ruiz-OrtegaMLorenzoORuperezMBlancoJEgidoJ. Systemic infusion of angiotensin II into normal rats activates nuclear factor-kappaB and AP-1 in the kidney: role of AT(1) and AT(2) receptors. Am J Pathol2001; 158: 1743–1756.
23.
YangLXLiuHGuoRW. Angiotensin II induces EMMPRIN expression in THP-1 macrophages via the NF-kappaB pathway. Regul Pept163: 88–95.
