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Effects of rosuvastatin on expression of angiotensin-converting enzyme 2 after vascular balloon injury in rats

Journal of Geriatric Cardiology 2013年第2期10卷 151-158页

作者： Yong-Hong Li Qi-Xin Wang Jing-Wei Zhou Xian-Ming Chu Yu-Lin Man Ping Liu Bei-Bei Ren Ting-Ru Sun Yi An Department of Cardiology Affiliated Hospital of Medical College Qingdao University Qingdao 266003 China

Objective To investigate the effects and mechanisms of rosuvastatin on angiotensin -converting enzyme 2 (ACE2) in the process of neointimal formation after vascular balloon injury in rats, and to explore the effects of ACE2 and rosuvastatin in restenosis. Methods Thirty-six Wistar rats were randomly allocated into three groups: control group (n = 12), surgery group (n = 12), and statin group (n = 12). Aortic endothelial denudation of rats was performed using 2F balloon catheters. At days 14 and 28 after injury, aortic arteries were harvested to examine the following. Intimal thickening was examined by hematoxylin and eosin staining. We measured angiotensin II (Ang II) and angiotensin 1-7 (Ang-[1–7]) levels by a radioimmunological method or enzyme-linked immunosorbent assay. Protein andmRNAexpression of ACE2 and Ang II type 1 receptor (AT1) were investigated by immunohistochemistry, Western blots, and Reverse transcriptase- polymerase chain reaction (RT-PCR). We measured changes in proliferating cell nuclear antigen (PCNA) by immunohistochemistry. The level of phosphorylated extracellular signal regulated kinase 1/2 (P-ERK1/2) was evaluated byWestern blotting. Results Proliferation of vascular smooth muscle cells (VSMC) and intimal thickening were higher at day 14 after vascular balloon injury in the surgery group compared with the control group. Proliferation of VSMC was decreased by day 28 after injury, while intimal thickening continued. With rosuvastatin treatment, the extent of VSMC proliferation and intimal thickening was reduced at day 14 and 28 after injury. Ang II and P-ERK levels were significantly increased, Ang-(1–7) levels were significantly decreased, mRNA and protein expressions of ACE2 were significantly decreased, and AT1 expression was significantly increased at days 14 and 28 after vascular balloon injury in the surgery group compared with the control group. PCNAexpression was higher in the surgery group than in the control group, and it was signif

关键词： Angiotensin converting enzyme 2 balloon injury Extracellular signal regulated kinase Rosuvastatin

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Effect of rosuvastatin on expression of angiotensin Ⅱ receptors in rat aortic endothelium after balloon injury

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South China Journal of Cardiology 2011年第1期12卷 49-55页

作者： LIU Ping LI Yong-hong CAI Shang-lang Affiliated Hospital of Qingdao University Medical College ofCardiology Qingdao 266003 China

Background It＇s established that Angiotensin Ⅱ and its receptors are involved in intimal hyperplasia after balloon injury and stent restenosis. Recent evidence also suggests that statins have some anti-intimal hyperplasia effects. In this study, the effect of Rosuvastatin on expression of angiotensin Ⅱ receptors in rat aortic endothelium after balloon injury is therefore investigated. Methods All 52 Wistar Kyoto rats were established to aorta injury models by 2F balloon catheter, then were randomly divided into sham operation group, aorta injury group and Rosuvastatin-treatment group. After 14 days, the aortic specimens of the animals were harvested and performed immunohistochemistry and determination of molecular biology. Results The results showed that （i） The 14 days-balloon injury induced obvious intima thickening （P 〈 0.01）, however, the phenomenon was reduced by 14 daystreatment with Rosuvastatin （P 〈 0.01）. （ii） The expressions of angiotention Ⅱ type Ⅰ （AT1） and type Ⅱ （AT2） receptor mRNA and protein were markedly up-regulated by the balloon injury （P 〈 0.01）, after 14 days-treatment with Rosuvastatin, the expression of AT1 receptor mRNA and its protein was decreased （P 〈 0.01）, but the expression of AT2 receptor mRNA and its protein was further increased （P 〈 0.05）. Conclusion In this study, we observed that the balloon injury induced-intima thickening was reduced by Rosuvastatin in rats, which might be linked with the regulation of expression of angiotensin Ⅱ receptors.

关键词： rosuvastatin balloon injury angiotention Ⅱ receptor

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Inhibitory effects of Icariside Ⅱ on Intimal Hyperplasia in Rat Carotid Arteries induced by balloon injury

Inhibitory effects of Icariside Ⅱ on Intimal Hyperplasia in...

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首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Luo Chao Li Yi qi Wang Jun yi Li Xiao tong Li Ye Li Lu Jun yuan Gao Yang Yang Dan li Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University

Objective:To research the effects of Icariside II(IcsII) on vascular intimal hyperplasia in balloon-injured carotid artery of rats and explore the possible ***:Fourty rats were randomly divided into the sham operation group(n=10)and other group(n=30).Animal carotid artery models were established with the balloon-injured in rats,and among them the survival rats(n=24) were randomly divided into three groups(n=8):model,IcsII-L,IcsII-H *** IcsII-L and IcsII-H groups were gavage administered with Ics(10,20 mg/kg/d) for 14 *** same volume distilled water was administered in sham group and model group for14 *** four hour after the last dose,the neointimal hyperplasia levels were observed in the injured side of the vessel with *** neointimal area(NIA) and intimal area/medial area(NIA/MA) were *** protein expression of p-NF-κB(p65)、TGF-β1、p-Smad3、IkBα、TNF-α、IL-6 in vascular were examined by Western Blot *** protein expression of p-NF-κB(p65),TGF-β1,p-Smad3,and IL-6 in vascular wall were examined by immunohistochemistry ***:Compared with the sham groups,the lumen area was reduced,and the NIA and NIA/MA were increased in model group(Pballoon-injury,and the possible mechanisms may be through the suppression NF-κB pathway and down-regulation of TGF-β/Smads pathways.

关键词： Icariside Ⅱ balloon injury intimal hyperplasia NF-κB TGF-β

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Involvement of stromal cell-derived factor-1α(SDF-1α),stem cell factor(SCF) and fractalkine(FKN) in Ginsenoside Rg1 protection against intimal hyperplasia in rat balloon injury

Involvement of stromal cell-derived factor-1α(SDF-1α),stem...

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首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Anling Hu Jiajia Liu Bo Huang Cancan Duan Jie Liu Lisheng Li Shangfu Xu Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education Zunyi Medical University

Background:Intimal hyperplasia is the major therapeutic concern after percutaneous coronary *** aim of this study is to investigate effects of Ginsenoside Rgl on intimal hyperplasia and the underling mechanisms through attenuating the expressions of stromal cell-derived factor-1α(SDF-1α)/CXCR4,stem cell factor(SCF)/c-kit and fractalkine(FKN)/CX3 ***:Rats were operated with carotid artery balloon *** treatment groups were gavaged with 8 and 16 mg/kg/d of Ginsenoside *** 14 days of treatment,carotid artery pathological changes were evaluated by *** expression ofα-SMA and PCNA were detected by double-label *** levels of SDF-1α,SCF and FKN were detected by enzyme linked immunosorbent *** protein expressions of SCF,SDF-1α and FKN,as well as the receptors c-kit,CXCR4 and CX3 CR1 were detected by ***:Ginsenoside Rg1 dose-dependently inhibited balloon injury-induced intimal hyperplasia,as evidenced by reducing neointima area(NIA),neointima area/media area(NIA/MA),neointima area/internal elastic area(NIA/IELA),and decreasing the protein expression of α-SMA and *** Rg1 reduced serum levels of SDF-1α,SCF and FKN, and it also decreased the protein expressions of SCF, SDF-1αand FKN,as well as the receptors c-kit,CXCR4 and CX3 ***:This study clearly demonstrated that Ginsenoside Rg1 was effective in inhibiting intimal hyperplasia,and this effect was mediated,at least in part,through the SCF/c-kit,SDF-1α/CXCR4 and FKN/CX3 CR1 axes.

关键词： balloon injury TSG SCF/c-kit SDF-1α/CXCR4 FKN/CX3CR1 Intimal hyperplasia

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Naringenin attenuates carotid restenosis in rats after balloon injury via RIP1-RIP3-MLKL signaling pathway

Naringenin attenuates carotid restenosis in rats after ballo...

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首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Huang Bo Hu An-ling Li Ying-ying Shi Wan-lan Huang Juan Jiang Qing-song Xu Shang-fu Wu Qin Li Li-sheng Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University Department of Pharmacology Chongqing Key Laboratory of Biochemistry and Molecular PharmacologyChongqing Medical University

Vascular restenosis has been proved as the major drawback of percutaneous coronary interventions(PCI) which is characterized of neointimal ***(Nar) is a kind of natural dihydroflavonoid with a variety of beneficial effects,including anti-oxidative,antibiosis,anti-cancer and anti-inflammatory properties,yet the underlying effects on vascular restenosis remain *** study aimed at investigating the effect of Nar on neointimal hyperplasia in the common carotid artery after balloon injury and the mechanisms underlying this *** male rats were operated with carotid artery balloon injury induced by a 2 F balloon,after which we harvested rats at 1,3,7 and 14 days to observe the pathological process of neointimal ***(25,50,100 mg/kg/d) or volume-matched CMC-Na were subsequently continuously administered to the rats by gavaging for 14 *** detection and histopathological examination shows that Nar dose-dependently inhibited balloon injury-induced intimal hyperplasia,as evidenced by reducing imima-media thickness,neointimal area(NIA),neointimal area/media area(NIA/MA) and neointimal area/internal elastic area(NIA/IELA),decreasing the protein expression of PCNA after 14 days' *** detecting the activities of superoxide dismutase(SOD) and the level of malondialdehyde(MDA)and glutathione(GSH),we found that Nar prevented balloon injury-induced oxidative *** results indicated that Nar significantly reduced overproduction of pro-inflammation cytokines including interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) post balloon ***,results of RT-qPCR demonstrated that RIP1,RIP3 and MLKL mRNA expression were further down-regulated after Nar treatment,which now be recognized as the key regulation of inflammation process in *** results suggested that Nar can suppress balloon injury-induced vascular neointimal hyperplasia by inhibit the release of inflammatory factors,which may

关键词： Naringenin Neointimal hyperplasia balloon injury Anti-inflammation RIP1-RIP3-MLKL signaling pathway

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Heparin-derived oligosaccharide inhibits vascular intimal hyperplasia in balloon-injured carotid artery

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Chinese Journal of Natural Medicines 2017年第6期15卷 442-450页

作者： LIU Jie-Ru WU Jie YU Xin-Chao QIAN Xuan XIONG Rui WANG Hui-Fang YU Dan-Feng LIU Fei-Fei HE Shu-Ying School of Life Science and Technology China Pharmaceutical University Nanjing 210009 China

The aims of the present study were to determine the effects of heparin-derived oligosaccharides(HDOs) on vascular intimal hyperplasia(IH) in balloon-injured carotid artery and to elucidate the underlying mechanisms of action. An animal model was established by rubbing the endothelia within the common carotid artery(CCA) in male rabbits. The rabbits were fed a high-cholesterol diet. Arterial IH was determined by histopathological changes to the CCA. Serum lipids were detected using an automated biochemical analysis. Expressions of mR NAs for vascular endothelial growth factor(VEGF), basic fibroblast growth factor(bF GF), vascular cell adhesion molecule-1(VCAM-1), monocyte chemoattractant protein-1(MCP-1), scavenger receptor class B type I(SR-BI), and ATP-binding cassette transporter A1(ABCA-1) were analyzed using reverse transcription polymerase chain reaction assays. Expressions of VEGF, VCAM-1, MCP-1, SR-BI and ABCA-1 proteins were analyzed by Western blotting. Enzyme-linked immunosorbent assays were used to quantify expression levels of VEGF and b FGF. Our results showed that administration of HDO significantly inhibited CCA histopathology and restenosis induced by balloon injury. The treatment with HDOs significantly decreased the m RNA and protein expression levels of VEGF, b FGF, VCAM-1, MCP-1, and SR-BI in the arterial wall; however, ABCA-1 expression level was elevated. HDO treatment led to a reduction in serum lipids(total cholesterol, triglycerides, high-density and low-density lipoproteins). Our results from the rabbit model indicated that HDOs could ameliorate IH and underlying mechanism might involve VEGF, b FGF, VCAM-1, MCP-1, SR-BI, and ABCA-1.

关键词： Atherosclerosis Heparin-derived oligosaccharide Intimal hyperplasia balloon injury

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Ginsenoside Rg1 inhibits vascular intimal hyperplasia in balloon-injured rat carotid artery by down-regulation of extracellular signal-regulated kinase 2

Ginsenoside Rg1 inhibits vascular intimal hyperplasia in bal...

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中国药理学会第十一次全国学术会议

作者： GAO Yang,DENG Jiang,YANG Dan-Li,GONG Qi-hai,HUANG Xie-Nan (Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province,Zunyi Medical College,Zunyi 563000,China)

Ginsenoside Rg1(Rg1),one of the main active components of Panax ginseng,has been demonstrated to inhibit proliferation of vascular smooth muscle cells(VSMCs) induced by tumor necrosis factor-αin *** present study is aimed to examine the possible effects of Rgl on vascular neointimal hyperplasia in balloon-injured carotid artery of rats in *** animal model was established by rubbing the endothelia with a balloon catheter in the common carotid artery(CCA) of male Sprague Dauley *** the rats were intraperitoneally injected with distilled water in model group and sham operation control,or with Rgl 4 mg·kg·d,8 mg·kg·d and 16 mg·kg·d in other balloon injured *** consecutive 14 d,the vascular intimal hyperplasia was evidenced by histopathological changes of the CCA and the protein expression of proliferating cell nuclear antigen(PCNA),a marker of the proliferation in VSMCs,and the phosphorylated extracellular signal-regulated kinase2(pERK2) as well as mitogen-activated protein kinase phosphatase-1(MKP-1) were examined by immunohistochemistry;the expressions of proto-oncogene(c-fos),ERK2 and SMα-actin mRNA were analyzed by Real-Time *** results demonstrated that Rgl administration could significantly ameliorate the histopathology of CCA and decrease the protein expression of PCNA induced by endothelia rubbing;and Rgl medication also significantly decreased the expressions of p-ERK2 protein,ERK2 and c-fos mRNA in vessel wall,but up-regulated the MKP-1 expression, which was reported to inactivate mitogen-activated protein kinase ***,Rgl could elevate the decreased SMα-actin mRNA expression induced by balloon *** is concluded that Rg1 can suppress the vascular neointimal hyperplasia induced by balloon injury,the mechanism may be involved in the inhibition on ERK2 signaling,and related,at least partly,to the increase in MKP-1 expression.

关键词： Ginsenoside Rg1 neointimal hyperplasia balloon injury extracellular signal-regulated kinase 2 mitogen-ativated protein kinase phosphatase-1

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