Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice

The incidence of cardiovascular disease is predicted to increase as the population ages. There is accumulating evidence that arginase upregulation is associated with impaired endothelial function. Here, we demonstrate that arginase II (ArgII) is upregulated in aortic vessels of aged mice and contributes to decreased nitric oxide (NO) generation and increased reactive oxygen species (ROS) production via endothelial nitric oxide synthase (eNOS) uncoupling. Inhibiting ArgII with small interfering RNA technique restored eNOS coupling to that observed in young mice and increased NO generation and decreased ROS production. Furthermore, enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxation responses to acetylcholine in aged vasculature were markedly improved following siRNA treatment against ArgII. These results might be associated with increased L-arginine bioavailability. Collectively, these results suggest that ArgII may be a valuable target in age-dependent vascular diseases.     

Determination of arterial wall shear stress

The arteries can remodel their structure and function to adapt themselves to the mechanical environment. In various factors that lead to vascular remodeling, the shear stress on the arterial wall induced by the blood flow is of great importance. However, there are many technique difficulties in measuring the wall shear stress directly at present. In this paper, through analyzing the pulsatile blood flow in arteries, a method has been proposed that can determine the wall shear stress quantitatively by measuring the velocity on the arterial axis, and that provides a necessary means to discuss the influence of arterial wall shear stress on vascular remodeling.     

Proteome Analysis of Aflibercept Intervention in Experimental Central Retinal Vein Occlusion

Aflibercept is a frequently used inhibitor of vascular endothelial growth factor (VEGF) in the treatment of macular edema following central retinal vein occlusion (CRVO). Retinal proteome changes following aflibercept intervention in CRVO remain largely unstudied. Studying proteomic changes of aflibercept intervention may generate a better understanding of mechanisms of action and uncover aspects related to the safety profile. In 10 Danish Landrace pigs, CRVO was induced in both eyes with an argon laser. Right eyes were treated with intravitreal aflibercept while left control eyes received isotonic saline water. Retinal samples were collected 15 days after induced CRVO. Proteomic analysis by tandem mass tag-based mass spectrometry identified a total of 21 proteins that were changed in content following aflibercept intervention. In retinas treated with aflibercept, high levels of aflibercept components were reached, including the VEGF receptor-1 and VEGF receptor-2 domains. Fold changes in the additional proteins ranged between 0.70 and 1.19. Aflibercept intervention resulted in a downregulation of pigment epithelium-derived factor (PEDF) (fold change = 0.84) and endoplasmin (fold change = 0.91). The changes were slight and could thereby not be confirmed with less precise immunohistochemistry and Western blotting. Our data suggest that aflibercept had a narrow mechanism of action in the CRVO model. This may be an important observation in cases when macular edema secondary to CRVO is resistant to aflibercept intervention.     

Matching Static and Dynamic Compliance of Small‐Diameter Arteries,with Poly(lactide‐co‐caprolactone) Copolymers: In Vitro and In Vivo Studies

Mechanical mismatch between vascular grafts and blood vessels is a major cause of smaller diameter vascular graft failure. To minimize this mismatch, several poly‐l ‐lactide‐co‐ε‐caprolactone (PLC) copolymers are evaluated as candidate materials to fabricate a small diameter graft. Using these materials, tubular prostheses of 4 mm inner diameter are fabricated by dip‐coating. In vitro static and dynamic compliance tests are conducted, using custom‐built apparatus featuring a closed flow system with water at 37 °C. Grafts of PLC monomer ratio of 50:50 are the most compliant (1.56% ± 0.31?mm Hg^?2), close to that of porcine aortic branch arteries (1.56% ± 0.43?mm Hg^?2), but underwent high continuous dilatation (87 µm min^?1). Better matching is achieved by optimizing the thickness of a tubular conduit made from 70:30 PLC grafts. In vivo implantation and function of a PLC 70:30 conduit of 150 µm wall‐thickness (WT) are tested as a rabbit aorta bypass. An implanted 150 µm WT PLC 70:30 prosthesis is observed over 3 h. The recorded angiogram shows continuous blood flow, no aneurysmal dilatation, leaks, or acute thrombosis during the in vivo test, indicating the potential for clinical applications.     

Comparative pharmacokinetic study of the components of Jia‐Wei‐Kai‐Xin‐San in normal and vascular dementia rats by ultra‐fast liquid chromatography coupled with tandem mass spectrometry

A fast, sensitive, and reliable ultra‐high performance liquid chromatography coupled with tandem mass spectrometry method has been developed and validated for simultaneous quantification of geniposide, polygalaxanthone III, 3,6′‐disinapoyl sucrose, α‐asarone, β‐asarone, poricoic acid A, poricoic acid B, dehydrotumulosic acid, deoxyschizandrin, schizandrin B, and kaempferide in plasma after oral administration of extracts of Jia‐Wei‐Kai‐Xin‐San in normal and vascular dementia rats. The developed method was precise and accurate within the linearity range of the analytes. The lower limits of quantification were 1.04–2.68 ng/mL for all the analytes. Both intra‐ and inter day precision and accuracy of the analytes were all within accepted criteria. The mean extraction recoveries of the analytes and the internal standard from rat plasma were all >60.0%. The validated method had been successfully applied to compare pharmacokinetic profiles of the analytes in plasma of normal and vascular dementia rat treated with herbal extracts. Results indicated that differences existed between normal and vascular dementia model rats except dehydrotumulosic acid and kaempferide, which might be due to the pathology of vascular dementia and pharmacological effect of the analytes. These pharmacokinetic studies might benefit for the mechanism exploration and clinical use of traditional Chinese medicine formulae.     

CTA成像在下肢血管闭塞病变中的应用及与血管腔内疗效的关系

本文探讨计算机体层扫描血管造影(CTA)检查在下肢血管闭塞病变中的应用价值及与血管腔内疗效的关系。选取经数字减影血管造影(DSA)确诊的93例下肢血管闭塞病变患者,采用CTA检查,分析CTA诊断病变部位结果、血管狭窄程度及与DSA诊断结果的一致性,并探讨CTA征象与患者血管腔内疗效的关系。结果显示,CTA诊断下肢血管闭塞病变部位、狭窄程度与DSA诊断结果均具有较高一致性(P<0.05);病变血管长度>1.41 cm、血管狭窄程度4级、病变血管远端CT值>62.65 Hu、钙化性斑块是下肢血管闭塞病变血管腔内治疗失败的危险因素(P<0.05)。CTA检查是诊断下肢血管闭塞病变的可靠方法,通过检查患者病变血管长度、血管狭窄程度、远端CT值及管腔内粥样斑块性质,有助于降低治疗盲目性,提高血管腔内治疗成功率。     

Review: Aptamers in microfluidic chips

This review, covering reports published from 2002 to August 2010, shows how aptamers have made significant contributions in the improvements of microfluidic chips for affinity extraction, separations and detections. Furthermore, microfluidic chip methods for studying aptamer-target interactions and performing aptamer selections have also been summarized. Accordingly, research vacancies and future development trends in these areas are discussed.     

Potential role of HMG CoA reductase inhibitor on oxidative stress induced by advanced glycation endproducts in vascular smooth muscle cells of diabetic vasculopathy

Advanced glycation endproducts (AGEs)-induced vascular smooth muscle cell (VSMCs) proliferation and formation of reactive oxygen species (ROS) are emerging as one of the important mechanisms of diabetic vasculopathy but little is known about the antioxidative action of HMG CoA reductase inhibitor (statin) on AGEs. We hypothesized that statin might reduce AGEs-induced intracellular ROS of VSMCs and analyzed the possible mechanism of action of statin in AGEs-induced cellular signaling. Aortic smooth muscle cell of Sprague-Dawley rat (RASMC) culture was done using the different levels of AGEs stimulation in the presence or absence of statin. The proliferation of RASMC, ROS formation and cellular signaling was evaluated and neointimal formation after balloon injury in diabetic rats was analyzed. Increasing concentration of AGEs stimulation was associated with increased RASMC proliferation and increased ROS formation and they were decreased with statin in a dose-dependent manner. Increased NF-κB p65, phosphorylated ERK, phosphorylated p38 MAPK, cyclooxygenase-2, and c-jun by AGEs stimulation were noted and their expression was inhibited by statin. Neointimal formation after balloon injury was much thicker in diabetic rats than the sham-treated group but less neointimal growth was observed in those treated with statin after balloon injury. Increased ROS formation, subsequent activation of MAPK system and increased VSMC proliferation may be possible mechanisms of diabetic vasculopathy induced by AGEs and statin may play a key role in the treatment of AGEs-induced diabetic atherosclerosis.     

Core-shell fibrous vascular grafts with the nitric oxide releasing property

Small-diameter vascular grafts with the nitric oxide(NO) releasing property were designed and prepared.Diazeniumdiolated N,N'-dibutyl-1,6-hexanediamine(DBHD/N2O2) was first synthesized as the NO donor and doped into the biocompatible polymer poly(ε-caprolactone)(PCL).The fibrous vascular grafts were fabricated by electrospinning.Despite the reduced platelet adhesion observed on the NO releasing grafts,the cytotoxicity and burst release were apparent,especially at a higher loading level of the NO donor.In or...