The development of an in vitro flow model of human saphenous vein graft intimal hyperplasia

1996 ◽  
Vol 31 (4) ◽  
pp. 607-614 ◽  
Author(s):  
K Porter
1996 ◽  
Vol 31 (4) ◽  
pp. 607-614 ◽  
Author(s):  
K. E. Porter ◽  
S. Nydahl ◽  
P. Dunlop ◽  
K. Varty ◽  
A. J. Thrush ◽  
...  

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Swastika Sur ◽  
Songcang Chen ◽  
Jeffrey T Sugimoto ◽  
Devendra K Agrawal

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.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Michael J Osgood ◽  
Kyle Hocking ◽  
Eric S Wise ◽  
Kevin W Sexton ◽  
Padmini Komalavilas ◽  
...  

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.


2018 ◽  
Vol 39 (suppl_1) ◽  
Author(s):  
M S Ruiter ◽  
G Garoffolo ◽  
M Piola ◽  
M Agrifoglio ◽  
M Zanobini ◽  
...  

2011 ◽  
Vol 666 (1-3) ◽  
pp. 150-157 ◽  
Author(s):  
Naciye Yaktubay Döndaş ◽  
Nehir Sucu ◽  
Banu Coşkun Yilmaz ◽  
Halil Mahir Kaplan ◽  
Murat Özeren ◽  
...  

2002 ◽  
Vol 21 (2) ◽  
pp. 212-217 ◽  
Author(s):  
W. Stooker ◽  
H.W.M. Niessen ◽  
W.R. Wildevuur ◽  
V.W.M. van Hinsbergh ◽  
J. Fritz ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Bulent Demir ◽  
Burak Onal ◽  
Sibel Ozyazgan ◽  
Esra Demir ◽  
Vedat Bakuy ◽  
...  

Objective. To study pitavastatin’s effects on nuclear factor-kappa B (NF-κB ) and adhesion molecules in human saphenous vein graft endothelial culture indicating its pleotropic properties. Materials and Method. Low-dose (0.1 μM/L) and high-dose (1μM/L) pitavastatin calcium were administered as a frontline therapy in human saphenous endothelial cell culture, followed by induction of inflammation by TNF-α and determination of mRNA level alterations of ICAM-1 and NF-κB genes of endothelial cells using the qRT-PCR method. Additionally, immunofluorescence method was used to show the expression of NF-κB and ICAM-1. Finally, LDH levels were determined by the ELISA method to quantify cytotoxicity. Results. ICAM-1 mRNA expression in the low-dose pitavastatin+TNF-α group was significantly higher than that in the TNF-α group and significantly lower than that in the high-dose pitavastatin+TNF-α group (for all comparisons, P = 0.001). The low-dose pitavastatin+TNF-α group had a similar NF-κB mRNA expression with TNF-α and high-dose pitavastatin+TNF-α groups. Conclusion. Pitavastatin increases ICAM-1 mRNA expression in saphenous vein endothelial cells. Furthermore, the effect of pitavastatin on adhesion molecules appears independent of NF-κB. Novel studies are needed in this field.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Anna C. Roberts ◽  
Jai Gohil ◽  
Laura Hudson ◽  
Kyle Connolly ◽  
Philip Warburton ◽  
...  

Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein- (SV-) EC were compared between T2DM and ND patients in parallel. Proliferation, migration, andin vitroangiogenesis assays were performed; western blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia, TNF-α, and palmitate) to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration (~30%) and angiogenesis (~40%) compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant inhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC function, but TNF-αand palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp.), effects mimicked by Akt inhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study highlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and long-term dysfunction to the homeostatic capacity of the endothelium.


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