冠状动脉药物涂层支架与置入后的血管再狭窄

背景：近年来随着药物涂层支架研究的增多及临床应用不断扩大,使冠状动脉内支架置入后再狭窄率显著降低,且在预防再狭窄中较裸支架具有独特应用价值。 目的：阐述药物涂层支架的临床应用进展,并探讨支架的涂层材料、类型与置入后再狭窄的关系及与宿主的相容性。 方法：作者以“冠脉支架,金属支架,药物涂层支架,再狭窄”为检索词,在中国期刊全文数据库及Medline 数据库中,采用电子检索的方式进行文献检索。排除Meta分析及重复性研究,共检索到27篇文献。 结果与结论：药物涂层支架的确是介入心脏病学的一项重要突破,使介入心脏病学进入了一个新的时代,但其远期效果仍需进一步观察。各种药物涂层支架所含药物或含量不同,其作用机制不同,而且药物释放的速率也不同,所以药物涂层支架临床应用后的效用和安全性需要由严谨和大量的临床研究来证实。现今药物支架的载体材料经过长时间的人体腐蚀,材料本身会老化、脱落,在血管组织内形成小块,从而可能引起晚期的不良反应。如果采用生物可降解的材料作为药物载体材料,那么就有可能减少晚期不良反应的出现。因此,开发一种理想的支架系统,目前主要的研究方向是可降解的低致炎性聚合物材料以及高效的药物控释体系。     

砷涂层支架置入后的血管组织相容性

背景：研究认为,三氧化二砷可以抑制血管平滑肌细胞的增殖,促进其凋亡,那么砷对血管平滑肌细胞的增生是否也有同样的抑制作用,砷涂层血管支架能否与血管组织相容,早期较好地被血管内膜覆盖或达到减少内膜过度增生的作用？ 目的：观察砷涂层血管支架的血管组织相容性。 方法：取大耳白家兔14只,随机分为2组,分别在腹主动脉处植入砷涂层316 L不锈钢支架和316 L不锈钢裸支架,植入28 d后结扎支架部位血管的远端和近端,取下支架部位的血管行苏木精-伊红染色,光镜检查。 结果与结论：①大体观察：支架处的血管外径稍大于相邻处血管的外径,呈扩张状态,无肉眼可见的血栓,切开支架,支架表面可见光滑的新生内膜形成,新生内膜表面光滑。②光镜观察：支架丝位于血管的中层,中层平滑肌被压,支架丝周边,血管内膜平滑肌增生,使血管内膜增厚。支架丝的血管腔面可见新生的血管内膜形成并覆盖支架丝,支架丝与血管组织之间可见一薄层黑色物质,为涂层药物砷及其化合物,证明砷涂层支架可以被血管组织覆盖,具有良好的血管组织相容性。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

心血管病患者药物涂层支架载入药物的筛选与应用

BACKGROUND: Drug-eluting stents have achieved better treatment outcomes, but late stent thrombosis shakes its status. With the development of drug-eluting stents, loaded drugs are the key to reduce stent thrombosis. OBJECTIVE: To analyze the screening and application of drug-eluting stents. METHODS: A computer-based search was performed for literatures published from 2010 to 2016 in databases of PubMed and WanFang using the keywords of “drug eluting stents; rapamycin (sirolimus); paclitaxel; heparin; zotarolimus; everolimus” in English and Chinese, respectively. According to inclusion and exclusion criteria, 30 eligible literatures were included for analysis. RESULTS AND CONCLUISON: An ideal drug-eluting stent can selectively inhibit vascular smooth muscle and is expected to be anti-coagulated, but makes no effects on vascular endothelial cells or promoting the cell proliferation. Most of the loaded drugs are antithrombotic and anti-proliferative drugs, among which, rapamycin-eluting and paclitaxel-eluting stents are extensively used. Regardless of delaying the proliferation of vascular endothelial cells and increasing the thrombosis risk, most of drug-eluting stents are still loaded with these two drugs, and only few stents loaded with rapamycin derivatives, such as everolimus, zotarolimus, tacrolimus and pimecrolimus. Current research focuses on developing a stent with rapid drug releasing and anti-proliferative capacity. Meanwhile, the combination of drugs and biphasic releasing are another novel idea.      

同种与不同种药物洗脱支架治疗后支架再狭窄的Meta分析

背景：冠心病患者发生药物洗脱支架再狭窄拟行再次支架置入治疗时选择何种类型药物支架尚无定论。 目的：对比同种及不同种药物洗脱支架在治疗冠心病患者首次置入药物洗脱支架后发生再狭窄的有效性和安全性。 方法：计算机检索1984年1月至2012年2月Pubmed数据库、EMBASE数据库、Cochrane图书馆、Google学术搜索及中国生物医学文献光盘等数据库中同种及不同种药物洗脱支架在治疗冠心病患者首次置入药物洗脱支架后发生再狭窄的临床试验,进行 Meta分析。 结果与结论：共纳入6篇,均包括首次置入药物洗脱支架后再次置入西罗莫司洗脱支架或紫杉醇洗脱支架的临床试验,共983例患者。同种与不同种药物洗脱支架处理首次药物洗脱支架置入后再狭窄在全因死亡(P=0.31,I²=14%,OR=0.92,95%CI[0.40,2.08])、再次心肌梗死发生(P=0.64,I²=0,OR=2.68,95%CI[1.00,7.24]、支架内血栓发生率(P=0.82,I²=0,OR=2.02,95%CI[0.37,11.08])及靶病变血管重建(P=0.63,I²=0,OR=1.15,95%CI[0.75,1.76])方面差异无显著性意义。提示同种与不同种药物洗脱支架治疗药物洗脱支架再狭窄的有效性及安全性无差异。     

药物涂层支架涂层的工艺

近年来,药物涂层支架的开发和应用得到了广泛的关注,被认为是心血管介入治疗领域内的一场革命。综述了近年来的药物涂层支架的制作工艺,并对各种工艺的优劣性做出了初步评价。     

两类药物洗脱支架药物释放曲线对血管壁内药物浓度影响的数值研究

研究两类药物释放曲线对血管壁中药物浓度分布的影响,为药物洗脱支架（DES）的优化设计提供依据;建立三维支架-血管模型,采用数值方法分析了雷帕霉素和紫杉醇两种药物释放曲线下血管壁中药物的浓度分布;初始药物释放率的增大会导致初始血管壁内药物浓度的增大,但随着时间的增加,血管壁中的药物浓度均趋于平稳。两种药物释放曲线下血管壁中的药物浓度均是随着时间的变化先增加后减少的,相比来说,雷帕霉素血管壁中的药物浓度随着时间变化的趋势要比紫杉醇血管壁中的药物浓度随着时间变化的趋势平稳,并且雷帕霉素血管壁中的药物浓度分布要比紫杉醇中血管壁中的药物浓度分布均匀。血管壁中药物浓度变化趋势的平稳性以及药物浓度分布的均匀性表明,雷帕霉素药物释放曲线要优于紫杉醇药物释放曲线。     

国产雷帕霉素药物涂层支架置入ST抬高型心肌梗死患者的近期预后

背景：冠状动脉药物涂层支架置入治疗是急性ST段抬高型心肌梗死的最佳治疗方法,但由于老年患者合并危险因素较多,死亡率随着年龄的增加而增高。 目的：观察不同年龄ST段抬高型心肌梗死患者置入国产雷帕霉素药物涂层支架的临床特征及住院期间预后特点。 方法：回顾性分析307例因初发ST段抬高型心肌梗死接受急诊冠状动脉国产雷帕霉素药物涂层支架置入治疗患者的临床资料,根据年龄分为3组,非老年组(< 65岁,n=175)、普通老年组(65-74岁,n=83)、高龄组(≥75岁,n=49),比较3组住院期间的临床特征、病死率及联合心血管事件发生情况。 结果与结论：与非老年组相比,普通老年组、高龄组女性比例较高(P < 0.05),吸烟者较少(P < 0.05),既往高血压病史比例增加(P < 0.05),血红蛋白、总胆固醇、三酰甘油、低密度脂蛋白胆固醇水平降低(P < 0.05)。随着年龄的增长,血清肌酐水平逐渐升高,恶性心律失常发生率与住院期间心源性死亡发生率逐渐增加。与非老年组、普通老年组比较,高龄组心功能Killip分级≥Ⅱ级比例、3支或左主干病变比例较高(P < 0.05),成功再灌注率下降(P < 0.05),急性充血性心力衰竭、联合心血管事件的发生率较高(P < 0.05)。多因素Logistic回归分析显示,年龄是患者住院期间病死率的独立危险因素(P < 0.01)。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

药物涂层支架的研究进展

药物涂层支架在介入心脏病治疗中存在着很大应用潜力,也是预防血管再狭窄的重要方法。首先论述了支架与血液相互作用的机理,分析了药物涂层支架缓释药物的基本原理,然后重点对药物涂层支架的缓释涂层、药物缓释体的设计以及药物涂层支架研究的最新进展进行了综合评述。     

药物涂层支架的研究进展

冠状动脉内安放支架具有操作简便、疗效明显等特点，但由于支架本身是一种金属异物．可以导致血栓的形成和引起机体的免疫反应。因而术后亚急性血栓形成和再狭窄仍是两大主要并发症。而药物涂层支架属于药物洗脱性聚合物涂层支架，即在金属支架表面涂以某种聚合物，并在此基础上结合一种有治疗作用的药物或抗体．将药物运送到病变部位提高局部药物浓度，达到治疗目的。本文综述了药物涂层支架相关问题的研究进展。     

药物涂层支架的研究进展

冠状动脉粥样硬化是导致人类因心脏病死亡的最主要原因，经皮冠状动脉成形术是其主要治疗手段，但是术后再狭窄的发病率高达10％-60％，目前大量研究表明，药物涂层支架能显著降低经皮冠状动脉成形术后再狭窄率，具有广阔的应用前景。就药物涂层支架的最新进展做一综述。     

TSC-36/FRP inhibits vascular smooth muscle cell proliferation and migration

OBJECTIVE: In-stent restenosis is a vascular proliferation/migration disorder characterized by hyperplasia of vascular smooth muscle cells (VSMCs). Because mounting evidence suggests that the therapeutic potential of anti-proliferation and anti-migration therapy, we investigated possible inhibitory effects of the matricellular protein TGF-beta-stimulated clone 36 (TSC-36) on vascular smooth muscle cell proliferation and migration in vitro and in vivo. METHODS: Human umbilical artery smooth muscle cells (SMCs) were treated with inducting agents daidzein or estradiol. TSC-36 expression was detected by nested competitive PCR and in situ hybridization. TSC-36 was expressed in Origami (DE3) cells. The recombinant protein was used to immunize rabbits to produce polyclonal antibodies. VSMCs were treated with various concentrations of recombinant TSC-36 (rTSC-36) protein and daidzein. The MTT assay was used to analyze for cell proliferation. A transwell system was used to detect cell migration. Flow cytometry was used to detect cell phase. A rat carotid artery balloon injury model was duplicated. The rats were treated with daidzein or solvent control. Animals were sacrificed 5 weeks later, and injured arteries were taken for pathology and histology. RESULTS: TSC-36 mRNA and protein expression was induced in SMCs. Cell proliferation and migration were inhibited by rTSC-36. rTSC-36 caused accumulation of SMCs in G2 phase. The inducting agent daidzein decreased neo-intima proliferation. TSC-36 mRNA and protein expression was induced and expressed in the neo-intima. CONCLUSION: TSC-36 can be induced in VSMCs and inhibits VSMCs proliferation in vitro and in vivo.     

血管平滑肌细胞凋亡在血管再狭窄中作用的研究进展

血管平滑肌细胞构成新生内膜增生的重要部分,且在血管腔内治疗术后再狭窄的心血管疾病的发生和发展中具有重要作用。血管平滑肌细胞凋亡能有效抑制血管球囊损伤和血管旁路移植术后新生内膜增生,从而可为血管术后再狭窄提供治疗手段。     

Tumor necrosis factor-alpha antibody eluting stents reduce vascular smooth muscle cell proliferation in saphenous vein organ culture

Expression of TNF-alpha a vascular smooth muscle cell (VSMC) mitogen, is up-regulated in injured/proliferating vessel wall. Coronary stents are tested worldwide for their use as local drug delivery devices to address vascular pathophysiology. In this study we have investigated the effect of TNF-alpha antibody eluting stents on VSMC proliferation in human saphenous vein (HSV) organ culture. The adsorption and elution characteristics of TNF-alpha antibody was assessed using stent wires. The stents adsorbed up to 0.25 microg of TNF-alpha antibody/mg of stent and showed a biexponential elution curve, with 34.4% (SD 4.4%) antibody remaining on the stent after 72 h of washing in a perfusion circuit. TNF-alpha antibody delivery from loaded stents to the vessel wall was assessed ex vivo. TNF-alpha and proliferating cell nuclear antigen (PCNA) expression in the vascular specimens was assessed by immunostaining or ELISAs. TNF-alpha ELISAs showed a significant increase in the cytokine levels from the vascular lysates prepared from proliferating tissue culture compared with fresh vein (P < 0.05). Immunohistochemical localization showed an increase in the PCNA positivity of VSMC from these cultures. PCNA staining was barely detected from the fresh tissue. However, a decrease in PCNA staining was observed from tissue sections of venous segments cultured with TNF-alpha antibody eluting stents. PCNA ELISAs demonstrated a 23.7% decline in the antigen levels from the day 7 tissue cultured with such loaded stents. In conclusion, activated VSMC in tissue culture showed an up-regulation of TNF-alpha cytokine, in association with an increase in the PCNA expression in the vessel wall. The local neutralization of this cytokine with TNF-alpha antibody eluting stents reduced VSMC proliferation in the wall. We suggest that TNF-alpha antibody eluting stents may limit restenosis in vivo, which may have important clinical benefits.     

Renal vascular smooth muscle proliferation in neurofibromatosis

An unusual vascular lesion was seen in a 14-year-old white boy with renal vascular hypertension and neurofibromatosis. Microscopically, nodular intimal and medial proliferations of spindle-shaped cells involved arteries, arterioles, and veins of all caliber within the renal parenchyma. Immunoperoxidase studies indicated these cells to have characteristics of smooth muscle, and this finding was confirmed by ultrastructural examination. Despite the generalized nature of the process in the biopsy sample, the patient's hypertension responded well to surgical treatment.     

Rap1 promotes proliferation and migration of vascular smooth muscle cell via the ERK pathway

Background

Rap1 is involved in a multitude of cellular signal transduction pathways, which has extensively been linked to cell proliferation and migration. It has been shown to be important in the regulation of physiological and pathological processes. The present study aims to elucidate its detailed mechanistic in proliferation and migration.

原花青素对同型半胱氨酸诱导的血管平滑肌细胞增殖、迁移的影响

目的： 探讨葡萄籽中的原花青素(GSP)对同型半胱氨酸(HCY)诱导的血管平滑肌细胞(VSMC)增殖、迁移的抑制作用及其机制。方法: 采用细胞计数及［3H］-TdR检测细胞增殖，用DCFH-DA、Western blotting法检测GSP对VSMC增殖、迁移的抑制作用及分析其相关的分子信号转导通路。结果: HCY浓度依赖性地诱导VSMC的增殖与迁移, 1 mmol/L HCY使VSMC的增殖与迁移分别比对照组升高3.9倍及4.1倍(P<0.01)；DCFH-DA结果显示, 1 mmol/L HCY使VSMC的活性氧(ROS)水平比对照组升高4倍(P<0.01)。而在不同浓度的GSP(5-20 g/L) 处理组，HCY诱导VSMC的增殖、迁移以及活性氧水平都被显著抑制(P<0.01)。在GSP 20 g/L 处理组，VSMC的增殖、迁移以及活性氧水平都接近空白对照组。与HCY组相比，GSP还显著降低HCY诱导VSMC MCP-1、IL-6及TNF-α的表达水平(P<0.01)。GSP还阻断HCY诱导的NF-κB的激活及显著降低NF-κB的活性(P<0.01)。结论: GSP通过抑制NF-κB的激活而抑制HCY诱导的血管平滑肌细胞增殖、迁移及炎症反应。     

Emerging regulators of vascular smooth muscle cell migration

Journal of Muscle Research and Cell Motility - Vascular smooth muscle cells (VSMCs) are the predominant cell type in the blood vessel wall and normally adopt a quiescent, contractile phenotype....     

人组织激肽释放酶基因重组腺病毒转染对血管平滑肌细胞增殖和迁移的影响

目的:探讨重组腺病毒介导的人组织激肽释放酶(hKLK1)基因转移对血小板源性生长因子-BB(PDGF-BB)诱导下的自发性高血压大鼠(SHR)血管平滑肌细胞(VSMCSHR)增殖和迁移的影响。方法:自行构建双顺反子重组腺病毒载体,携带强绿色荧光蛋白(EGFP)标志基因和目的基因hKLK1;用细胞计数法和四甲基偶氮唑盐(MTT)比色法检测细胞增殖,流式细胞仪检测细胞生长周期;蛋白免疫印迹法(Western blotting)测定细胞周期素依赖性激酶抑制蛋白p27Kip1、p21Cip1的表达。采用改良Boyden微孔膜双槽法测定VSMCSHR迁移。结果:(1)hKLK1基因转移呈感染复数依赖性(20-100MOI)抑制PDGF-BB诱导的VSMCSHR生长,100MOI时抑制率为39.3%;呈时间依赖性抑制VSMCSHR生长,第5d时达高峰,抑制率为35.2%。(2)hKLK1基因转移可显著抑制PDGF-BB诱导的VSMCSHR增殖,峰值抑制率为30.2%(P0.01);细胞周期阻滞于G0/G1期的VSMCSHR明显增多,最大阻滞率为36.4%(P0.01),而缓激肽B2受体特异性阻断剂Hoe140逆转了hKLK的抑制作用。(3)hKLK1基因转移明显上调PDGF-BB诱导VSMCSHR的p27Kip1、p21Cip1表达,Hoe140明显降低p27Kip1、p21Cip1表达。(4)hKLK1基因转移可明显抑制PDGF-BB诱导的VSMCSHR细胞迁移,抑制率为34.6%,且Hoe140不影响该抑制作用。结论:hKLK1基因转移可抑制PDGF-BB诱导的VSMCSHR增殖,主要由缓激肽B2受体介导的,通过上调细胞周期素依赖性激酶抑制蛋白p27Kip1、p21Cip1表达的途径。而hKLK1基因转移抑制VSMCSHR迁移效应可能不通过B2受体。