Autogenous inside-out versus standard vein and skeletal muscle-combined grafting for facial nerve repair

BACKGROUND： In the repair of nerve defects, collapse of the venous wall, as a result of vein grafting alone, could impede nerve regeneration. Therefore, vein lumens filled with muscle and nerve segments have been used to bridge nerve defects. OBJECTIVE： To compare the effects of autogenous, inside-out, vein-skeletal, muscle-combined grafting versus standard, vein-skeletal, muscle-combined grafting for the repair of facial nerve defects. DESIGN, TIME AND SETTING： A randomized, controlled, neuroanatomical, animal study was performed at the Animal Experimental Center and Laboratories of the Capital Medical University Xuanwu Hospital and the Peking Union Medical College Hospital from September 2007 to October 2008.MATERIALS： A total of 10 healthy, male, New Zealand rabbits, aged 6 months, were randomly assigned to inside-out, vein-skeletal, muscle-combined grafting and standard, vein-skeletal, muscle-combined grafting groups, with 5 rabbits in each group. METHODS： A 20-mm gap in the buccal branch of the right facial nerve was made in each animal, which was respectively repaired with inside-out, vein-skeletal, muscle-combined grafts or standard vein-skeletal muscle-combined grafts.MAIN OUTCOME MEASURES： At 6 months after implantation, evoked maximal compound muscle action potentials were recorded on bilateral facial nerves using electromyogram. Myelinated nerve fibers of the regenerating nerves were quantified using myelin sheath osmic acid staining. RESULTS： There was no significant difference between the groups in terms of ratios of bilateral amplitude and latency of compound muscle action potential （P 〉 0.05）. Moreover, morphology of regenerating nerves and quantity of myelinated nerve fibers were similar between the groups （P 〉 0.05）. CONCLUTION： Compared with standard vein grafting, the inside-out vein grafting did not significantly improve nerve regeneration. Therefore, it is not necessary to utilize inside-out vein grafting for the repair of nerve defects, in particular with the combined use of autogenous vein and skeletal muscle grafts.

Internal Jugular Vein Graft after Inadvertent Severing of the Internal Carotid Artery during Carotid Endarterectomy and an Urgent Re-Exploration for Immediate Post-Operative Wound Site Bleeding: A Case Report

Carotid endarterectomy is a well-established treatment for preventing stroke in selected patients. Although there is debate over whether patch angioplasty or primary closure should be used to reconstruct the bifurcation after carotid endarterectomy, there is growing evidence in the literature in favor of patch angioplasty. When compared to primary closure, patch angioplasty during conventional carotid endarterectomy is suggested to lower the incidence of restenosis and recurrent ipsilateral stroke. Various materials have been used as a patch in this procedure, including the saphenous vein, synthetic patches, or less frequently, an internal jugular vein patch where extensive narrowing of the internal carotid artery is evident. In our case, we used an internal jugular vein graft after inadvertent severing the internal carotid artery (ICA) during carotid endarterectomy after the failure of reconstruction with a saphenous vein patch. We also encountered immediate postoperative reactionary hemorrhage following anesthetic reversal, necessitating an urgent re-exploration. The purpose of this case report is neither an attempt to suggest all patients need angioplasty nor to state that an internal jugular vein patch or graft is superior to synthetic material or saphenous veins;rather, it is an attempt to emphasize a potentially effective rescue way to reconstruct inadvertent extensive vascular injury during carotid endarterectomy.

Management of the middle hepatic vein and its tributaries in right lobe living donor liver transplantation

BACKGROUND: Left liver graft from a small donor will not meet the metabolic demands of a larger adult recipient. To overcome the problem of graft size insufficiency, living donor liver transplantation (LDLT) using the right lobe has become a standard method for adult patients. As the drainage of the median sector (segments V, VIII and IV) is mainly by the middle hepatic vein (MHV), the issue of whether the MHV should or should not be taken with the graft or whether the MHV tributaries (V5, V8) should be reconstructed in the recipient remains to be settled. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1985-2006) on right lobe living donor liver transplantation, middle hepatic vein, vein graft, hepatic venoplasty and other related subjects. RESULTS: Some institutions had proposed their policy for the management of the MHV and its tributaries. Dominancy of the hepatic vein, graft-to-recipient weight ratio, and remnant liver volume as well as the donor-to-recipient body weight ratio, the volume of the donor's right lobe to the recipient's standard liver volume and the size of MHV tributaries are the major elements for the criteria of inclusion of the MHV, while for the policy of MHV tributaries reconstruction, the proportion of congestive area and the diameter of the tributaries are the critical elements. Optimal vein grafts such as recipient's portal vein and hepatic venoplasty technique have been used to obviate hepatic congestion and venous drainage disturbance. CONCLUSIONS: Taking right liver grafts with the MHV trunk (extended right lobe grafts) or performing the MHV tributaries reconstruction in modified right lobe grafts, according to the criteria proposed by the institutions with rich experience, can solve the congestion problem of the right paramedian sector and help to improve the outcomes of the patients. The additional use of optimal vein grafts and hepatic venoplasty also can guarantee excellent venous drainage.

Evaluation of corporal fibrosis in cadaveric pericardium and vein grafts for tunica albuginea substitution in rats

<abstract>Abstract Aim: To evaluate the degree of corporal fibrosis in rats with cadaveric pericardium or vein as grafting materials for tunica albuginea substitution. Materials and methods: Thirty male Sprague-Dawley rats (300 g-325 g) were divided at random into 3 groups of 10 animals each: group 1 was the sham-operated controls and groups 2 and 3 underwent wedge excision of tunica albuginea and replacement with cadaveric pericardium and vein grafts, respectively. Four months later, rats were sacrificed and the penis removed to assess the degree of fibrosis using RT PCR technique for TGP-β1 mRNA expression. The tissues were fixed in 10 % formalin, paraffin-embedded and stained with Masson's trichrome and Verhoff's van Giesen for collagen and elastic fibers. Results: Four months after grafting, there was minimal fibrosis surrounding the patch in the vein graft rats and moderate fibrosis in the pericardial graft rats. The degree of penile fibrosis in the pericardial graft rats was significantly higher than that in the controls (P<0.01), but in the vein graft rats it was not significantly different from that of the controls (P>0.05). Conclusion: The degree of penile fibrosis of cadaveric pericardial graft was significantly higher than that of the control group, while in the vein graft group it was comparable to the latter. The authors believe that the vein graft may be a more ideal substance to be used as the tunica albuginea substitute than the pericardial graft in the surgical treatment of Peyronie's disease.

Experimental Study of Tissue-type Plasminogen Activator Gene to Prevent Vein Grafts Stenosis

The effects of in vivo local expression of recombined human tissue-type plasminogen activator （t-PA） gene on the thrombosis and neointima formation of vein grafts were explored. Jugular vein-to-artery bypass grafting was performed on 72 New Zealand white rabbits. The rabbits were divided into 3 groups according to the different processing methods： transfected t-PA gene group （n = 24）, vector group （n= 24） and blank control group （n = 24）. Samples of vein grafts were harvested at different time points after surgery. The expression of t-PA gene in vein graft was detected by RT-PCR and the synthesis of t-PA protein by Western-Blot assay. The t-PA activity was measured by chromogenic substrate assay. The Cr51 labeled platelets accumulation in vein grafts was counted. The histopathological changes were compared in intima hyperplasia index among the three groups after operation. The results showed that at the 2^nd , 5^th , 14^th and 28^th day after operation, RT-PCR and Western-blot confirmed the expression of t-PA mRNA and protein at the site of gene transfer. The t-PA activity detected on the 2^nd, 5^th, 14^th and 28^th day in experimental group was 370. 63±59. 44, 344. 13±48. 47, 252.87±51.80 and 161.75±68. 94 U/g respectively, and disappeared on the 60^th day and undetected in the control groups. The number of platelets accumulated in the vein grafts in gene group, vector group and blank control group was （85. 04 ± 21.58） 10s, （225.87±85.13） 10^6 and （211.57±78.02） 10^6 respectively. The number of platelets accumulated in gene group was significantly fewer than that in the control groups. Morphometric analysis revealed that intimal hyperplasia was markedly reduced in the t-PA gene group as compared with that in the control groups. It was suggested that the local expression of t-PA gene in vein graft significantly inhibited the accumulation of platelets, thrombosis and concomitant intimal hyperplasia, by which stenosis of bypass graft could be prevented effectively.

Glabridin Relaxes Vascular Smooth Muscles by Activating BK_(Ca) Channels and Inhibiting Phosphodiesterase in Human Saphenous Vein

The aim of the current study was to investigate the pharmacological activity of glabridinon the isolated human saphenous vein (SV) and explore the underlying mechanisms. Samples of patients' SVs were removed during bypass surgery, and 4-mm lengths of the vessels were placedin Krebs solution at ±4℃ and hung in an isolated organ bath to assess their contraction/relaxationresponses. The contraction/relaxation responses were recorded to observe if the cyclic guanosinemonophosphate (cGMP)/protein kinase G (PKG) pathway mediates the relaxant effect of glabridinafter treatment with blockers like ODQ (a guanylate cyclase inhibitor), KT5823 (a PKG inhibitor),isobutylmethylxanthine [IBMX, a phosphodiesterase (PDE) inhibitor], and cantharidin [Cant,a myosin light-chain phosphatase (MLCP) inhibitor]. Moreover, nitric oxide (NO), cGMP, andPKG levels in SV tissues were determined by ELISA after incubation with glabridin, N(o)-nitro-L-arginine methyl ester (L-Name, a NO synthetase inhibitor), phenylephrine (PE), ODQ, IBMX,and KT5823. The results showed that glabridin relaxed the vascular smooth muscle of humanSV pretreated with PE in a dose-dependent manner, which was independent of the endothelium.The vasorelaxant effect of glabridin was only inhibited by iberiotoxin (IbTX), Cant, and KT5823.Glabridin increased cGMP and PKG levels in SV homogenates, whereas it did not alter the NOlevel. The enhancing efects of cGMP and PKG levels by glabridin were abolished by ODQ andKT5823. In conclusion, glabridin has a vasorelaxant effect, which is associated with the activationof BKc. channels and inhibition of PDE.

Emergency re-routing of anterior sector venous outflow for right lobe living donor liver transplantation including the middle hepatic vein

BACKGROUND:Controversy remains over whether the middle hepatic vein should be included in the liver graft in right liver living donor liver transplantation.Congestion in the anterior sector of a right liver graft can cause graft malfunction,which is especially devastating in the case of a graft with marginal size in relation to recipient body size on top of poor pre-transplant recipient status.The case we report here highlighted the importance of the middle hepatic vein in right liver living donor liver transplantation.METHODS:We illustrated the rectification of outflow obstruction of the middle hepatic vein in the anterior sector of right liver graft caused by technical error during transplantation.The rectification was performed with emergency re-routing using an artificial conduit.RESULT:Congestion in the anterior sector of the graft improved immediately and the patient’s postoperative liver function test results improved gradually.CONCLUSIONS:The middle hepatic vein is important for effective drainage of the anterior sector of a right liver graft.The re-routing technique described in the report can also be applied to cases in which the middle hepatic vein is injured during hepatectomy requiring immediate reconstruction.

Reducing intimal hyperplasia in vein grafts harvested by a no-touch harvesting technique

Objective To investigate the effect of no-touch harvesting technique in reducing vein graft intimal hyperplasia. Methods This longitudinal trial compared graft angiostenosis of two groups undergoing jugular vein to carotid artery interposition grafting in rabbit model. Conventional group:12 rabbits had their veins stripped,distended,and stored in heparinized saline solution. No-touch group:12 rabbits had veins removed with surrounding tissues,but were not distended,and stored in heparinized blood. The grafts were removed 4 weeks following grafting,and morphometry and immunohistochemistry assessment were performed. Results The intimal thickness,degree of angiostenosis and proliferation index of vascular smooth muscle cells of no-touch group were significantly reduced (P<0.01) compared with those of the conventional group. The proliferating cell nuclear antigen positive-staining cells were significantly increased (P<0.01) in the conventional group compared with whose in the no-touch group. Conclusion Harvesting the vein graft with no-touch harvesting technique could significantly reduce intimal hyperplasia of the vein graft.

Differentially Expressed MicroRNAs Associated with Vein Graft Restenosis in Rats

Objective:Intimal hyperplasia is the main cause of restenosis of vein grafts after venous transplantation.MicroRNAs are considered to play a role in vein graft restenosis;however,the expression profi le of microRNAs in neointima has not been reported in detail.We wanted to investigate the differentially expressed microRNAs in the restenosis of vein grafts in rats.Methods:We established a rat model for vein transplantation to explore the pathogenic roles of microRNAs during intimal hyperplasia.Hematoxylin and eosin staining was used to confi rm intimal hyperplasia in the vein grafts.Changes in microRNA expression in the vein grafts were detected 3 and 14 days after surgery by sequencing,reverse transcription–quantitative polymerase chain reaction,and bioinformatics analyses for functional annotation.Results:We detected 711 newly predicted microRNAs among all the comparisons.Among these comparisons,437 differentially expressed microRNAs were detected in the postoperative day 3 group versus the control group,265 were detected in the postoperative day 14 group versus the control group,and 158 were detected in the postoperative day 14 group versus the postoperative day 3 group.Pathway analysis revealed signifi cant enrichment of target genes that mediate Wnt,mitogen-activated protein kinase,vascular smooth muscle contraction,and regulation of actin cytoskeleton signaling.Conclusion:Our results provide insight into the pathogenesis of restenosis and will help develop novel targets in the prevention and treatment of vein graft restenosis.

Effects of 3,3',4',5,7-pentamethylquercetin on intimal hyprerplasia vein grafts

Objective Pentamethylquercetin (PMQ) has a role in cardiovascular protection.We investigate the effects of 3,3 ’,4 ’,5,7 pentamethylquercetin,a derivative of PMQ,on intimal hyperplasia of the vein grafts in rats both in vivo and in vitro. Methods The proliferation of vascular smooth muscle cells (VSMC) was induced with Ang Ⅱ (0.1 μmol/L,24 h) while PMQ was administrated at six different dosages (0.1,0.3,1,3,10 and 30 μmoL/L).

Outflow reconstruction with arterial patch in domino liver transplantation: a new technical option

Domino liver transplantation（LT）, using livers from familial amyloidotic polyneuropathy（FAP） patients, is a well described technique useful to expand donor pool. One of the main difficulties of this type of LT arises from the necessity to share the vascular pedicles between the graft and the donor. The most important challenge resides in restoring a proper hepatic venous outflow in the FAP-liver recipient.This is specially challenging when using the piggy-back technique, because the hepatic stumps may be too short. To overcome this issue, surgeons explored several techniques using different types of venous grafts. We describe a new technical option by using an arterial graft from the deceased donor. By using both iliac arteries a long graft is created and sutured as needed to the hepatic vein stump. We describe herein this new technique employed in a domino liver recipient who underwent retransplantation for ischemic cholangitis. The procedure was performed using the piggy-back technique; the venous stump of the FAP liver was reconstructed with the arterial graft. The patient had uneventful postoperative and mid-term hepatic function, and anastomosis was patent 24 months after LT.

Percutaneous coronary intervention of totally occluded coronary venous bypass grafts:An exercise in futility?

BACKGROUND Percutaneous coronary intervention(PCI)of diseased saphenous vein grafts(SVG)continues to pose a clinical challenge.Current PCI guidelines give a class III recommendation against performing PCI on chronically occluded SVG.However,contemporary outcomes after SVG intervention have incrementally improved with distal protection devices,intracoronary vasodilators,drug-eluting stents,and prolonged dual antiplatelet therapy.AIM To reassess the procedural and long-term outcomes of PCI for totally occluded SVG with contemporary techniques.METHODS This was a retrospective observational study conducted at a single university hospital.The study population consisted of 35 consecutive patients undergoing PCI of totally occluded SVG.Post-procedure dual antiplatelet therapy was continued for a minimum of one year and aspirin was continued indefinitely.Clinical outcomes were assessed at a mean follow-up of 1221±1038 d.The primary outcome was freedom from a major adverse cardiac event(MACE)defined as the occurrence of any of the following:death,myocardial infarction,stroke,repeat bypass surgery,repeat PCI,or graft reocclusion.RESULTS The study group included 29 men and 6 women with a mean age of 69±12 years.Diabetes was present in 14(40%)patients.All patients had Canadian Heart Classification class III or IV angina.Clinical presentation was an acute coronary syndrome in 34(97%)patients.Mean SVG age was 12±5 years.Estimated duration of occlusion was acute(<24 h)in 34%of patients,subacute(>24 h to 30 d)in 26%,and late(>30 d)in 40%.PCI was initially successful in 29/35 SVG occlusions(83%).Total stent length was 52±35 mm.Intraprocedural complications of distal embolization or no-reflow occurred in 6(17%)patients.During longer term follow-up,MACE-free survival was only 30%at 3 years and 17%at 5 years.CONCLUSION PCI of totally occluded SVG can be performed with a high procedural success rate.However,its clinical utility remains limited by poor follow-up outcomes.

Iatrogenic Disruption of Left Main Coronary Artery during Aortic Valve Replacement

This aortic valve replacement (AVR) remains the gold standard for symptomatic aortic stenosis. Peri-operative complications like dissection, stenosis involving coronary artery are well described in many series. We present a rare iatrogenic complication of disrupted left main coronary artery during the delivery of cardioplegia while performing AVR in a 54 year male patient for severe calcific aortic stenosis. The inadvertent injury to the artery was timely noticed and managed successfully with long saphenous vein graft.

The role of prourokinase gene in protecting vein grafts from intimal hyperplasia

Objective To study the duration of prourokinase gene expression in vein grafts and the role of the prourokinase gene in protecting vein grafts from neointimal hyperplasia.Methods Fifty-four Wistar rats were used in this study. In each rat, the jugular vein was excised and distended for 30 minutes using a solution containing either Adv5-CMV (control group) or Adv5-CMV/ Pro-UK (treatment group). Next, the jugular vein was reversed and interposed into the divided carotid artery of the same rat. On the 14th day after transfection, vein grafts of the control group were collected in order to perform a fibrinolysis test for prourokinase (Pro-UK) activity. On the 2nd, 7th, 14th, 28th, and 60th day, the vein grafts of the treatment group were likewise collected in order to detect prourokinase activity. On the 28th day, the vein grafts of both groups were explanted to evaluate the 3H-TDR incorporation so that pathologic analysis could be performed.Results Pro-UK activity could not be detected in the control group, while in the treatment group, the Pro-UK activity could be detected from the 2nd day onwards, peaking on the 7th day and declining from the 14th day, but yet persisting at a low level for a further month. The amount of 3H-TDR incorporated in the control group was higher than that in the treatment group. Pathologic analysis demonstrated that vein grafts of both groups exhibited wall thickening, but that the degree of graft neointimal hyperplasia and reduction of the graft lumen was greater in the control group than that in the treatment group. The occlusion rate of grafts in the control group was 20%. All grafts in the treatment group were patent.Conclusions Pro-UK gene transfer before vein grafting in vitro results in a high level of gene expression in the vein graft from the 7th day to 14th day. And its gene expression in the vein graft could reduce neointimal hyperlasia in the vein graft.

Effect of external stents on prevention of intimal hyperplasia in a canine vein graft model

Background External stents have been used to reduce intimal hyperplasia of vein grafts. The aim of the present study was to define the size of an external stent appropriate for a particular graft by comparing vein grafts with different sizes of external stents. Methods A series of paired trials was performed to compare femoral vein grafts with different sizes of external stents, where 30 modeled canines were equally divided into three groups： 6-mm external stent vs non-stent control, 4-mm vs 6-mm external stent, and 4-mm vs 8-ram external stent. At day 3 after operation, color Doppler flow imaging （CDFI） was done to observe blood flow in the lumen. Four weeks later, CDFI was re-checked and the veins were harvested, stained and measured. Results All grafts were patent without formation of thrombosis. External stents significantly reduced intimal thickness of the vein grafts with a 6-mm external stent compared with the vein grafts without external stents （P〈0.05）.The vein grafts with the 4-mm external stent had similar intimal, medial and adventitial thicknesses compared with those with the 6-mm external stent and the 8-mm external stent. Conclusions External stents can reduce intimal hyperplasia of vein grafts. Stents of different diameters exert the similar effect on prevention of intimal hyperplasia.

Perivenous application of fibrin glue prevents the early injury of jugular vein graft to arterial circulation in rabbits

Background Placement of an external support has been reported to prevent intimal hyperplasia of vein grafts. However, it is limited by potential complications. In the present study, we investigated the effect of fibrin glue on preventing vein graft failure as perivenous application. Methods Twenty-four rabbits were divided into non-supported group （n=12） and fibrin glue group （n=12）. All animals underwent unilateral jugular vein into common carotid artery interposition grafting and then fibrin glue was applied as perivenous support. Samples of tissues were harvested after 4 weeks. Results The vein grafts with fibrin glue demonstrated a statistically significant decrease in proliferating cell nuclear antigen in the medial/intimal region [13.38% （11.26%-15.11%）] compared with non-supported vein grafts [31.22% （27.15%-35.98%）] （P〈0.001）. Light microscopy showed remarkable attenuation of endothelial cell loss and numerous microvessels in neoadventitia in the fibrin glue group compared with the non-supported group. The smooth muscle cells migrated into adventitia significantly in fibrin glue group, whereas the smooth muscle ceils migrated into intima in non-supported group. Conclusion Perivenous support of vein graft with fibrin glue in vivo can attenuate the severe injury encountered in the non-supported vein grafts exposed to artery.

Promoting Vasa Vasorum Neovascularization of Vein Grafts Extenuates Hypoxia of the Wall and Its Subsequent Influence on Intimal Hyperplasia

Background： The autologous saphenous vein is the most common conduit for coronary artery bypass grafting, but the vein graft disease will occur. This study used Matrigel basement membrane matrix with many different growth factors to promote vasa vasorum neovascularization and extenuate the hypoxia to improve remodeling. Methods： This study observed the hypoxia and thickness of the vein grafts at different times. Normal veins and vein grafts with 15 min ofischemia one day postoperatively were harvested in the neck of rabbits. Paired vein grafts with 15 min ischemia bilaterally （control vs. Matrigel basement membrane matrix） were performed and harvested at 2, 6, and 12 weeks postoperatively. The rabbits were randomly divided into four postoperative groups （six rabbits in each group）： Group 1, one day postoperatively; Group 2, 2 weeks postoperatively; Group 3, 6 weeks postoperatively; and Group 4, 12 weeks postoperatively. The dimensions of vessel wall were captured, and the mean thicknesses of intima, media, and adventitia were measured. The hypoxia-inducible factor （HIF）- 1α and HIF-2ot labeling indices ofintima, media, and adventitia were also measured. Results： In Group 1, the labeling index of HIF-1α was high in the normal vein and decreased significantly in the vein grail one day postoperatively （intima： 80 4- 3% vs. 12 4- 1%, P = 0.01 ; media： 67 ±5% vs. 11 ± 1%, P = 0.01 ; adventitia： 40 ± 10% vs. 7 ±2%, P = 0.03）. The labeling index of HIF-2α had similar trend as HIF-1α （intima： 80 ± 10% vs. 10 ± 5%, P = 0.02; media： 60± 14% vs. 12 ± 2%, P = 0.01 ; adventitia： 45±20% vs. 10±4%, P = 0.03）. Compared with the control vein gratrol vein grafts with Matrigel basement membrane matrix had lower labeling indices of HIF-1α and HIF-2α in media and adventitia at Group 2 （HIF-1α： 34 ± 5% vs. 20 ±4%, P = 0.04 for media： 23 ± 3% vs. 11 ± 2%, P = 0.03 for adventitia; HIF-2α： 37 ± 6% vs. 21 ± 4%, P = 0.03 for media; 24 ±4% vs. 13 ± 2%, P = 0.04 for adventitia） and Group 3 （HIF-1α： 33 ± 4% vs. 7 ± 2%, P = 0.04 for media; 13 ± 3% vs. 3± 1%, P = 0.02 for adventitia; HIF-2α： 27 ± 4% vs. 12 ± 3%, P = 0.02 for media; 19 ± 2% vs. 6 ± 1%, P = 0.02 for adventitia）. There were no differences in mean thickness of intima, media, and adventitia between bilateral vein grafts at 2, 6, and 12 weeks postoperatively. Conclusions： This study indicated that promoting vasa vasorum neovascularization of vein grafts extenuated hypoxia, but did not influence the intimal hyperplasia of the wall,

MiR-551b-5p Contributes to Pathogenesis of Vein Graft Failure via Upregulating Early Growth Response-1 Expression

Background： Vein graft failure （VGF） is a serious complication of coronary artery bypass graft, although the mechanism remains unclear. The study aimed to investigate the effects of microRNAs （miRNAs） on the endothelial dysfunction involved in VGF. Methods： Human umbilical vein endothelial cells （HUVECs） were subjected to mechanical stretch stimulation to induce endothelial dysfunction. Genome-wide transcriptome profiling was performed using the Human miRNA OneArray＂ V4 （PhalanxBio Inc., San Diego, USA）. The miRNA-messenger RNA （mRNA） network was investigated using gene ontology and Kyoto Encyclopedia of Genes and Genomes. The miR-55 1b-5p mimic and inhibitor were applied to regulate miR-55 lb-5p expression in the HUVECs. The 5-ethynyl-2＇-deoxyuridine assay, polymerase chain reaction （PCR）, and Western blotting （WB） were used to assess HUVECs proliferation, mRNA expression, and protein expression, respectively. The vein graft model was established in early growth response （Egr）-I knockout （KO） mice and wide-type （WT） C57BL/6J mice for pathological and immunohistochemical analysis. Endothelial cells isolated from the veins of WT and Egr-1 KO mice were subjected to mechanical stretch stimulation; PCR and WB were conducted to confirm the regulatory effect of Egr- 1 on Intercellular adhesion molecule （loam-1）. One-way analysis of variance and independent t-test were performed for data analysis. Results： Thirty-eight rniRNAs were differentially expressed in HUVECs after mechanical stretch stimulation. The bioinforrnatics analysis revealed that Egr-1 might be involved in VGF and was a potential target gene of miR-551b-5p. The mechanical stretch stimulation increased miR-55 1b-5p expression by 2.93 ± 0.08 told （t= 3.07, P 〈 0.05）, compared with the normal HUVECs. Transfection with the miR-551b-5p mimic or inhibitor increased expression of miR-551b-5p by 793.1 ± 171.6 fold （t = 13.84, P 〈 0.001） or decreased by 26.3% ± 2.4% （t= 26.39, P 〈 0.05） in the HUVECs, respectively. HUVECs proliferation and EGR-I mRNA expression were significantly suppressed by inhibiting miR-551b-5p expression （P 〈 0.05）. The lumens of the vein grafts in the Egr-1 KO mice were wider than that in the WT mice. lcam-I expression was suppressed significantly in the Egr-1 KO vein grafts （P 〈 0.05）. Conclusions： Increased miR-55 1b-5p expression leads to endothelial dysfunction by upregulating Egr-1 expression. EGR-1 KO can improve the function of a grafted vein through suppressing loam-1.

Effects and mechanisms of non-restrictive external stent for prevention of vein graft restenosis in a rabbit model

Background Among various treatments preventing vein graft restenosis, external stent is receiving more and more attention. This study aimed to investigate the effect of non-restrictive external stent on the prevention of vein graft restenosis and the potential mechanisms of platelet-derived growth factor （PDGF） in the process of restenosis.Methods Thirty-six ＂New Zealand white rabbits＂ were randomly divided into two groups, stented group （group S） and control group （non-stented group, group NS）. Each rabbit underwent a reversed autologous external jugular vein into common carotid artery bypass grafting. In group S, the vein grafts were surrounded by a non restrictive stent which was 6 mm in diameter （a kind of Dacron vascular prosthesis）; and in group NS, there was no stent to support the vein grafts.The grafts were harvested at the first week （1W）, second week （2W） and fourth week （4W） after surgery respectively. The dimensions （including the thickness and area of the intima and media, luminal area） were measured by computer-aided image analysis system, and the intimal hyperplasia ratio was defined as the percentage of the area enclosed by the internal elastic lamina occupied by the intima.Results At 1W, the difference of the thickness and area of the intima between groups S and NS was not significant （P 〉0.05）; at 2W and 4W, the thickness and area of the intima and the intimal hyperplasia ratio in group S were less significant than those in group NS （P 〈0.05）; from 1W to 4W, the thickness and area of the media in group S were smaller than those in group NS （P〈0.05）. Immunocytochemistry staining of PDGF-B showed that the percentage of positive cells of intima in both two groups was peaked at 2W, and a significantly smaller percentage was detected in group S compared with that in group NS at 2W and 4W （P 〈0.05）; the percentage of PDGF-B positive cells of media in both two groups was also peaked at 2W, and that in group S was smaller than that in group NS from 1W to 4W （P 〈0.05）; and the percentage of PDGF-B positive cells of adventitia in group S was peaked at 4W, whereas the percentage of adventitia in group NS peaked at 2W, and the percentage of adventitia in group S was greater than in group NS at 4W （P 〈0.05）.Conclusions Non-restrictive external stenting inhibits the hyperplasia of the intima and media of the vein grafts and reduces the thickness and area of the intima and media; Non-restrictive external stenting inhibits the synthesis of PDGF and changes its distribution, and then inhibits the hyperplasia of the intima.