血管外膜在动脉粥样硬化中的作用

动脉粥样硬化被认为是受损的内皮细胞释放粘附因子,吸引单核细胞粘附浸润到内膜下吞噬脂质,同时平滑肌细胞进行增殖迁移并形成新生内膜的过程,但目前越来越多的证据提示血管外膜作为反应的先导者从外向内参与了这一过程。在诸多血管疾病模型中,均能检测到外膜的早期激活。成纤维细胞作为血管外膜的主要细胞成分,在血管损伤早期会进行增殖迁移至中膜和内膜,还可以通过释放活性氧、各种细胞因子、基质金属蛋白酶等来影响炎症反应,导致内膜增生,最终促进了血管重塑及一些心血管疾病的发生。因此,越来越多的研究关注外膜成纤维细胞对于动脉粥样硬化、糖尿病、腹主动脉瘤等疾病中的作用及其机制,本文对该领域新近研究进展做一综述。     

Krüppel样因子5介导血管平滑肌细胞的增殖和迁移

Krüppel样因子5（krüppel-like factor 5,KLF5）是KLF家族中与胚胎发育、细胞增殖和肿瘤发生密切相关的转录调节因子。为观察KLF5在体外培养的大鼠血管平滑肌细胞（vascularsmooth muscle cells,VSMCs）增殖和迁移活性中的作用,通过构建KLF5腺病毒表达载体并感染细胞以过表达KLF5或用特异性siRNA敲低KLF5,用MTT、流式细胞术以及免疫细胞化学染色和伤口愈合实验检测其对VSMCs增殖和迁移活性的影响。结果发现,KLF5过表达可加速细胞由G0/G1期向S期转变,促进细胞增殖和迁移;反之,敲低KLF5后细胞增殖活性明显低于转染无关序列NS-siRNA对照组细胞,G0/G1期细胞数所占比例增多,S期细胞数所占比例减少,VSMCs迁移活性也明显降低。结果表明KLF5可参与介导VSMCs的增殖和迁移。     

血小板源性生长因子对血管平滑肌细胞效应的机制研究进展

血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖及迁移是动脉粥样硬化(arteriosclerosis,AS)、支架后再狭窄(in-stent restenosis,ISR)发生、发展中共同的病理过程。血小板源性生长因子(platelet-derived growth factor,PDGF)是一种强效的促有丝分裂剂,在VSMCs增殖及迁移过程中具有重要作用。本文综述PDGF的生物学作用及其促进VSMCs增殖及迁移的机制研究新进展,特别是通过抑制该靶点对VSMCs增殖及迁移的意义。     

整联蛋白调控血管新生内膜增生的研究进展

血管新生内膜增生是支架植入术、动静脉瘘术等血管手术以及动脉粥样硬化、高血压等心血管疾病的生理特征。整联蛋白介导的细胞黏附在新生内膜增生过程中起着重要作用。该文概述了整联蛋白在此过程中对白细胞黏附、平滑肌细胞迁移增殖、再内皮化的调控及目前用于研究新生内膜的相关动物模型。了解整联蛋白调节血管新生内膜增生的分子机制,为临床上防治新生内膜增生、解决术后血管再狭窄等相关研究提供参考。     

Notch信号通路在血管损伤修复中的作用

Notch信号通路是进化中高度保守的信号转导通路,其调控细胞增殖、分化和凋亡的功能涉及几乎所有组织和器官。血管损伤后,Notch信号通路分子表达改变,引起内皮细胞（endothelial cell,EC）和血管平滑肌细胞（vascular smooth muscle cell,VSMC）表型改变,其增殖、迁移、抗凋亡等能力也随之变化,从而参与血管的损伤修复。Notch信号通路能够促进EC和VSMC增殖以及VSMC迁移至内膜,并提高其存活能力,凶此能够促进新生内膜的形成。     

在体导入NOS基因可抑制球囊扩张术后血管内膜增生

在体导入ＮＯＳ基因可抑制球囊扩张术后血管内膜增生血管平滑肌细胞（ＶＳＭＣ）增生、内膜增厚是球囊扩张术后再狭窄的主要发病机制之一。近年来许多实验表明ＮＯ有抑制培养ＶＳＭＣ增殖的作用;口服ＮＯ前体Ｌ－精氨酸可减轻内皮损伤诱导的血管内膜的增生。Ｌ－精氨酸在...     

平滑肌22α蛋白在血管稳态和血管重构中的作用

有关血管稳态和重构的分子机制一直是近年来的研究热点,也被视为治疗血管损伤性疾病的突破点.大量研究证实,血管损伤修复及病理性重构过程与血管平滑肌细胞(vascular smooth muscle cells,VSMCs)的表型转化、异常增殖与迁移、细胞衰老关系密切.平滑肌22α(smooth muscle 22α,SM2...     

不同浓度血府逐瘀汤含药血清对大鼠血管平滑肌细胞增殖、迁移及侵袭的影响

目的观察不同浓度血府逐瘀汤含药血清对大鼠主动脉平滑肌细胞（VSMCs）增殖、迁移及侵袭的影响,以及其生成一氧化氮（NO）的情况。方法用MTT法观察VSMCs的增殖,Transwell小室法观察VSMCs的迁移、侵袭,并检测培养上清液一氧化氮（NO）的含量。结果与空白对照组比较,5%血府逐瘀汤组能显著促进VSMCs的增殖（P〈0.05）,20%,30%血府逐瘀汤组能显著抑制VSMCs的增殖（P〈0.05）;与空白对照组比较,培养48 h的培养上清液中,血府逐瘀汤组的NO水平有显著升高（P〈0.01）,且与血府逐瘀汤含药血清的浓度有剂量依赖关系。结论低浓度（〈10%）血府逐瘀汤含药血清有促进VASMCs增殖和迁移、侵袭的作用,高浓度（〉10%）血府逐瘀汤含药血清有抑制VASMCs增殖、迁移和侵袭的作用,其作用可能与上清液的NO水平有关。     

干扰素调节因子家族

干扰素调节因子（IRFs）是调节干扰素（IFN）、干扰素刺激性应答基因（ISG）及其它相关基因表达的重要转录因子,通过调节IFN、ISG和其它密切相关基因表达而发挥多种生物学效应.     

C-myc反义RNA抑制血管平滑肌细胞增生的实验研究

观察血管内膜损伤后C－myc反义RNA在抑制血管平滑肌细胞的增生、迁移及防止动脉粥样硬化形成和血管再狭窄中的作用。选雄性日本大白兔36只,经球囊造成腹主动脉内膜损伤的同时,局部给予C－myc反义RNA、正义RNA及盐水,高胆固醇喂养12周处死,测量内膜厚度,计数增生细胞核抗原PCNA阳生细胞数。结果显示：盐水及正义对照组内膜明显增厚（317μm）,PCNA核阳性细胞数明显增多（63％）,可见明显的粥样斑块灶形成,而反义RNA治疗组内膜增厚仅为217μm,PCNA阳性细胞为30.5%,明显低于对照组,P＜0.01。结果表明：C－myc反义RNA具有显抑制VSMC增生,减轻粥样斑块形成的作用。     

Studies on microRNAs that are correlated with the cancer stem cells in chronic myeloid leukemia

Vascular remodeling is characterized by the aggregation of vascular smooth muscle cells (VSMCs) in intima. Previous studies have demonstrated that dehydroepiandrosterone (DHEA), a steroid hormone, can reverse vascular remodeling. However, it is still far clear that whether and how DHEA participates in the modulation of VSMCs activation and vascular remodeling. VSMCs were obtained from the thoracic aorta of SD rats. Cell proliferation was evaluated by CCK-8 assay and BrdU assay. To measure VSMCs migration activity, a transwell chamber assay was performed. Quantitative real-time RT-PCR and western blot were used to explore the molecular mechanisms. ROS generation by VSMCs was measured by DCF fluorescence. NADPH oxidase activity and SOD activity were measured by the corresponding kits. NF-κB activity was detected by NF-κB luciferase reporter gene assay. A rat carotid artery balloon injury model was built to evaluate the neointimal formation, and plasma PGF2 was measured by ELISA. Our results showed that DHEA significantly inhibited VSMCs proliferation after angiotensin (Ang II) stimulation by down-regulation of NADPH oxidase activity and ERK1/2 phosphorylation. Ang II can increase IL-6 and MCP-1 expression, but DHEA reverses these changes via inhibiting p38-MAPK/NF-κB (p65) signaling pathway. DHEA has no significant effects on VSMCs phenotype transition, but can reduce the neointimal to media area ratio after balloon injury. DHEA can alleviate oxidative stress and inflammation in VSMCs via ERK1/2 and NF-κB signaling pathway, but has no effect on VSMCs phenotype transition. Furthermore, DHEA attenuates VSMCs activation and neointimal formation after carotid injury in vivo. Taken together, DHEA might be a promising treatment for vascular injury under pathological condition.     

l-Theanine attenuates neointimal hyperplasia via suppression of vascular smooth muscle cell phenotypic modulation

Neointimal hyperplasia is a prominent pathological phenomenon in the process of stent restenosis. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play major pathological processes involved in the development of restenosis. l-Theanine, one of the major amino acid components in green tea, has been reported to improve vascular function. Here we display the effects of l-theanine on neointima formation and the underlying mechanism. In the rat carotid-artery balloon-injury model, l-theanine greatly inhibited neointima formation and prevented VSMCs from a contractile phenotype switching to a synthetic phenotype. In vitro study showed that l-theanine significantly inhibited PDGF-BB-induced VSMC proliferation and migration, which was comparable with the effect of l-theanine on AngII-induced VSMC proliferation and migration. Western blot analysis demonstrated that l-theanine suppressed PDGF-BB and AngII-induced reduction of SMA and SM22α and increment of OPN, suggesting that l-theanine inhibited the transformation of VSMCs from contractile to the synthetic phenotype. Further experiments showed that l-theanine exhibits potential preventive effects on neointimal hyperplasia and related vascular remodeling via inhibition of phosphorylation of Elk-1 and activation of MAPK1. The present study provides the new experimental evidence that l-theanine has potential clinical application as an anti-restenosis agent for the prevention of restenosis.     

A new role for Nogo as a regulator of vascular remodeling

Although Nogo-A has been identified in the central nervous system as an inhibitor of axonal regeneration, the peripheral roles of Nogo isoforms remain virtually unknown. Here, using a proteomic analysis to identify proteins enriched in caveolae and/or lipid rafts (CEM/LR), we show that Nogo-B is highly expressed in cultured endothelial and smooth muscle cells, as well as in intact blood vessels. The N terminus of Nogo-B promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle (VSM) cells, processes necessary for vascular remodeling. Vascular injury in Nogo-A/B-deficient mice promotes exaggerated neointimal proliferation, and adenoviral-mediated gene transfer of Nogo-B rescues the abnormal vascular expansion in those knockout mice. Our discovery that Nogo-B is a regulator of vascular homeostasis and remodeling broadens the functional scope of this family of proteins.