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KMID : 0648320090150010025
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Journal of The Korean Society of Hypertension
2009 Volume.15 No. 1 p.25 ~ p.34
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Effect of HMC05, a herbal extract, on collagen synthesis in vascular smooth muscle cells
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Lee Ji-Yeun
Lee Jo Woon Yi
Choi Jin-Yong
Kim Joo-Yun
Lee Bok-Soo
Shin Heung-Mook
Park Jeong-Euy
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Abstract
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Background and aim : Atherosclerosis is a chronic inflammatory disease. Once infiltrated monocytes or smooth muscle cells (SMCs) in the atherosclerotic lesions are activated, they produce many proteases, which destroy the structure of arterial wall and induce apoptosis of the SMCs by detaching them from the extracellular matrix (ECM). In this study, we tried to find the possible antiatherogenic mechanism of HMC05, which is the water extract of 8 herbs and is proven to have anti-atherosclerotic effect in the apoE-/-mice.
Methods: Apo E-/-mice were fed a high fat, high cholesterol diet (HFHC, 0.35% cholesterol) for 10 weeks with and without co-treatment of HMC05 (200 mg/kg). Aortic sinus sections from apoE-/-mice were stained and analyzed with masson trichrome or specific antibodies for individual collagen types followed by confocal analysis. In vitro study was done on human aortic smooth muscle cells. Role of heat shock protein (HSP27) on collagen expression was studied by using HSP27 siRNA followed by RT-PCR analysis.
Results: While total collagen content in atherosclerotic lesions caused by HFHC in apoE -/- mice was increased, it was not affected by HMC05 administration although the destruction of smooth muscle layer was significantly prevented. Confocal analysis revealed that HMC05 increased collagen type IV expression but not collagen type I and III expression in aortic sinus. However, in vitro study showed that HMC05 induced collagen type III by confocal analysis and type IV by RT-PCR analysis but not other collagen types or other ECM including fibrillin. HMC05 also did not affect metalloproteinases and tissue inhibitor metalloprotein expression. Proliferation of smooth muscle cells in atherosclerotic lesions were also inhibited by HMC05 in vitro as well as in vivo. HMC05 induced HSP27 expression in vitro. When HSP27 expression was knock-downed using specifically designed siRNA, oxidized low density lipoprotein induced-collagen type IV expression was significantly reduced.
Conclusions : HMC05 increased expression of collagen type III and IV and HSP27 in the atherosclerotic lesion of apoE -/- mice. HSP27 might play a key role via regulating collagen type IV expression in the pathogenesis of atherosclerosis. It also inhibited the proliferation of smooth muscle cells. This might affect the interaction with proteases, collagenases and extracellular matrix but needs to be further investigated.
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KEYWORD
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Atherosclerosis, HMC05, Collagen, Extracellular matrix (ECM), Heat shock protein 27 (HSP27)
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