Inhibition Effect of Arresten Gene Transfection Combined with Nanoparticle-Mediated ENDOSTAR on Intimal Hyperplasia in Autogenous Vein Graft in Rats

2020 ◽  
Author(s):  
Zhao-Xuan Liu ◽  
Jing Yu ◽  
Kai Cao ◽  
Qing-Yi Meng
Keyword(s):  
Intimal Hyperplasia ◽  
Vein Graft ◽  
Gene Transfection ◽  
Inhibition Effect ◽  
Autogenous Vein

scholarly journals Transfected Early Growth Response Gene-1 DNA Enzyme Prevents Stenosis and Occlusion of Autogenous Vein GraftIn Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Chengwei Liu ◽  
Xuesong Zhang ◽  
Shi Wang ◽  
Mingxun Cheng ◽  
Chuanyu Liu ◽  
...  
Keyword(s):  
Intimal Hyperplasia ◽  
Vein Graft ◽  
Growth Response ◽  
Early Growth ◽  
Response Gene ◽  
Vsmc Proliferation ◽  
Early Growth Response ◽  
Early Growth Response Gene ◽  
Autogenous Vein ◽  
Stenosis And Occlusion

The aim of this study was to detect the inhibitory action of the early growth response gene-1 DNA enzyme (EDRz) as a carrying agent by liposomes on vascular smooth muscle cell proliferation and intimal hyperplasia. An autogenous vein graft model was established. EDRz was transfected to the graft vein. The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR andin situhybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses. EDRz was located at the media of the vein graft from 2 to 24 h, 7 h after grafting. The Egr-1 protein was mainly located in the medial VSMCs, monocytes, and endothelium cells during the early phase of the vein graft. The degree of VSMC proliferation and thickness of intima were obviously relieved compared with the no-gene therapy group. EDRz can reduce Egr-1 expression in autogenous vein grafts, effectively restrain VSMC proliferation and intimal hyperplasia, and prevent vascular stenosis and occlusion after vein graft.

Smooth muscle cells in porcine vein graft intimal hyperplasia are derived from the local vessel wall

2011 ◽  
Vol 20 (3) ◽  
pp. e91-e94 ◽  
Author(s):  
Marc Jevon ◽  
Tahera I. Ansari ◽  
Jonathan Finch ◽  
Mustafa Zakkar ◽  
Paul C. Evans ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Intimal Hyperplasia ◽  
Vein Graft ◽  
Vessel Wall ◽  
Muscle Cells

EFFECT OF E2F DECOY OLIGODEOXYNUCLEOTIDES GENE THERAPY ON INTIMAL HYPERPLASIA IN EXPERIMENTAL VEIN GRAFT

2004 ◽  
Vol 78 ◽  
pp. 428-429
Author(s):  
W H. Cho ◽  
S O. Lee ◽  
S K. Baik ◽  
H T. Kim ◽  
I K. Lee
Keyword(s):  
Gene Therapy ◽  
Intimal Hyperplasia ◽  
Vein Graft

Abstract 184: Polo Like Kinase 1 Regulates Smooth Muscle Cell Proliferation in the G2-M Phase in Human Coronary Artery Bypass Conduits

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Swastika Sur
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Coronary Artery Bypass ◽  
Intimal Hyperplasia ◽  
Vein Graft ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Histone H3 ◽  
G2 Phase

Proliferation of smooth muscle cells (SMCs) and the resultant intimal hyperplasia cause coronary artery bypass graft (CABG) failure. Internal mammary artery (IMA) graft is immune to intimal hyperplasia (IH), but a saphenous vein graft is prone to develop neointima. The fate of SMCs is determined by the balance between the mitogenic and anti-mitogenic signals. Mitosis of SMCs through the cell cycle involves crossing the two restriction (R)-points in G1 and G2 phase, respectively. Upon loss of proper G1/S control, cells will progress into the G2-phase where G2 R-point can prevent cell proliferation. In this study, we examined the effect of mitogenic PDGF-BB stimulation on the G2 R-point and its relationship with the phosphorylation of PLK1, Cdc2 and Histone H3 in isolated SMCs of human bypass graft conduits. We observed increased expression and phosphorylation of PLK1 in PDGF-stimulated SV-SMCs compared to control SMCs without the treatment. Furthermore, PLK1 was phosphorylated and activated for a longer period of time in PDGF-stimulated SV- than IMA-SMCs. PLK1 m-RNA level was higher in PDGF-stimulated SV-SMCs than IMA. An ATP-competitive inhibitor of PLK1 attenuated PDGF-BB-induced proliferation in IMA and SV-SMCs. Cell proliferation was measured using cell count and immunoblotting against phospho-Histone H3 (pHistone) at Ser-10. Treatment with PLK1 inhibitor reduced PDGF-induced Cdc2 activation. Silencing the PLK1 gene by siRNA transfection of SV- and IMA-SMCs significantly reduced the expression of pHistone. These data demonstrate differential activity of PDGF-BB-induced PLK1, which was quantitatively and temporally greater in SV-SMCs than in the IMA. PLK1 inhibitor completely blocked the phosphorylation of PLK1 and attenuated proliferation in SV-SMCs. This in part, could suggest that PLK1 plays a critical role in the development of neointimal hyperplasia in SV grafts following CABG. Thus, inhibition of PLK1 activity could be a target in developing better therapeutic approach to prevent vein-graft disease.

Abstract 15922: Role of Polo-Like Kinase-1 in Intimal Hyperplasia in Saphenous Vein Graft: Potential Implication in Vein-Graft Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Swastika Sur ◽  
Songcang Chen ◽  
Jeffrey T Sugimoto ◽  
Devendra K Agrawal
Keyword(s):  
Coronary Artery ◽  
Saphenous Vein ◽  
Intimal Hyperplasia ◽  
Vein Graft ◽  
Saphenous Vein Graft ◽  
Bypass Graft ◽  
Fold Increase ◽  
Potential Implication ◽  
Vein Graft Disease ◽  
Graft Disease

Coronary revascularization by coronary artery bypass grafting (CABG) is the choice of procedure in patients with multi-vessel or left main coronary artery disease. Concerns have been raised on the long term result of CABG using saphenous vein graft (SVG) as its patency significantly declines following surgery, compared to internal mammary artery (IMA), which is almost immune to restenosis. Proliferation of smooth muscle cells (SMCs) is the key event in the pathogenesis of intimal hyperplasia leading to SVG failure. PDGF-BB is a major growth factor released at the site of pulsatile stretch- and shear stress-induced graft injury. Here, we examined, for the first time, the expression of PLK1 and its phosphorylation/activation in isolated human bypass graft conduits. Human SV and IMA vessels were freshly collected, SMCs isolated and cultured up to 5th passage. In cultured SMCs, effect of PDGF-BB was examined on total and phosphorylated PLK1 (pPLK1) by Western blot analysis. Cell proliferation was measured using thymidine incorporation, MTT method and cell count. We found significantly higher expression of pPLK1 and total PLK1 in PDGF-stimulated SV SMCs than IMA. SV SMCs had 5-fold increase in the density of pPLK1 and had 2-fold increase in the density of total PLK1. While in the IMA SMCs, increase in pPLK1 was significantly lower than in SV SMCs. Also, this increase was not sustained. These data suggest a greater and sustained sensitivity of SV SMCs to PDGF-BB induced PLK1 activity than that of IMA. A PLK1 blocker inhibited PDGF-induced proliferation in both IMA and SV SMCs. These data demonstrate differential activity of PDGF-induced PLK1 activation, which was greater in SV SMCs than in IMA. This could explain the development of intimal hyperplasia in SV conduits than the IMA following CABG. Thus, inhibition of PLK1 could be a target in developing better therapeutic approach to prevent vein-graft disease.

Abstract 293: Clinical Predictors of Endothelial Function in Human Saphenous Vein

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Michael J Osgood ◽  
Kyle Hocking ◽  
Eric S Wise ◽  
Kevin W Sexton ◽  
Padmini Komalavilas ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Saphenous Vein ◽  
Intimal Hyperplasia ◽  
Vein Graft ◽  
Graft Failure ◽  
Univariate Analysis ◽  
Clinical Predictors ◽  
Human Saphenous Vein ◽  
Graft Harvest ◽  
Vein Graft Failure

BACKGROUND: Human saphenous vein (HSV) remains the most widely utilized conduit for vascular bypass procedures. Outcomes remain limited by vein graft failure and intimal hyperplasia. Endothelial function is considered an important determinant of vein graft failure. We have observed significant variability in endothelial function in freshly isolated HSV samples. We therefore evaluated clinical predictors of endothelial function in HSV. Methods: We obtained freshly isolated HSV samples from the operating room immediately following harvest from patients undergoing coronary artery bypass procedures from Vanderbilt University Hospital and the Nashville VA Hospital. We obtained HSV samples prior to any intraoperative manipulations. HSV viability, smooth muscle function, and endothelial-dependent relaxation (EDR) were measured in a muscle bath. We collected the following clinical and demographic information: age, height, weight, gender, ethnicity, medical comorbidities, laboratory values (creatinine, HbA1c, lipids), ejection fraction, preoperative medication regimen, and method of vein graft harvest. We performed a univariate and multivariate analysis of predictors of endothelial function in HSV. Results: HSV samples were obtained from 149 patients. HSV EDR varied from -11% to 63%. Open harvest was employed for 39 HSV samples, compared with endoscopic harvest in 110 HSV samples. On univariate analysis, only open harvest was a statistically significant predictor of endothelial function (p=0.02): mean HSV EDR was 21.5% in HSV samples harvested open, compared with 15.4% in HSV harvested with an endoscopic technique. HSV EDR was also improved with preoperative aspirin use: mean HSV EDR was 18% in patients with preoperative aspirin use compared with 11.6% in patients who were not administered preoperative aspirin in a multivariate model when controlling for method of vein graft harvest (p=0.05). Conclusions: Endoscopic vein graft harvest is associated with endothelial dysfunction in HSV, while preoperative aspirin use is associated with improved endothelial function. Further work will be necessary to determine whether these factors are associated with development of intimal hyperplasia and vein graft failure.

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