Use of Brilliant Blue FCF during vein graft preparation inhibits intimal hyperplasia

Objective The human saphenous vein (HSV) is the most effective conduit for infrainguinal peripheral bypass grafting. Optimal vein graft preparation is critical to vein graft patency. Graft marking using surgical skin markers is detrimental to endothelial and smooth muscle function of the graft. The objective of this study was to evaluate the effect of FD&C Brilliant Blue No. 1 (FCF) as an alternative for vein graft marking. Methods Segments of HSV were collected after typical harvest and graft preparation. The tissues were cut into rings and either left unmarked or marked with FCF (2.6 mM). The functional viability of the rings was determined in a muscle bath. Results Marking with FCF did not impair contractility of the smooth muscle (Figure 1A). Contractility was restored in HSV segments that had no functional contractile responses after harvest and preparation (Figure 1B). To determine the mechanism of this protective effect of FCF, purinergic receptors were activated with BzATP with and without pre-incubation with FCF (50μM) or a purinergic receptor antagonist (oATP, control) and the rise in [Ca 2+ ] i was measured. FCF and oATP reduced the BZATP-evoked rise in [Ca 2+ ] i (Figure 1C), suggesting that the salutary effects of FCF were due to inhibition of a P2X or P2Y receptor. Conclusions FCF is a non-toxic alternative to surgical skin markers that antagonizes purinergic receptors in HSV. FCF restored functional viability to injured vascular smooth muscle. FCF may protect HSV against injury-elicited ‘danger’ signals such as extracellular ATP that is released during injury-induced preparation.

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Evaluating Differences in Transport Behavior of Sodium Chloride and Brilliant Blue FCF in Sand Columns

Transport in Porous Media ◽

10.1007/s11242-015-0551-4 ◽

2015 ◽

Vol 109 (3) ◽

pp. 765-779 ◽

Cited By ~ 1

Author(s):

Jiazhong Qian ◽

Yanan Wu ◽

Yong Zhang ◽

Yong Liu ◽

Yuehan Lu ◽

...

Keyword(s):

Sodium Chloride ◽

Brilliant Blue ◽

Transport Behavior ◽

Brilliant Blue Fcf

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

Cardiovascular Pathology ◽

10.1016/j.carpath.2010.04.003 ◽

2011 ◽

Vol 20 (3) ◽

pp. e91-e94 ◽

Cited By ~ 10

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

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

Transplantation Journal ◽

10.1097/00007890-200407271-01148 ◽

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

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Active transport of brilliant blue FCF across the Drosophila midgut and Malpighian tubule epithelia

10.1101/771675 ◽

2019 ◽

Author(s):

Dawson B.H. Livingston ◽

Hirva Patel ◽

Andrew Donini ◽

Heath A. MacMillan

Keyword(s):

Traumatic Injury ◽

Malpighian Tubule ◽

Malpighian Tubules ◽

Brilliant Blue ◽

Barrier Dysfunction ◽

Concentration Gradients ◽

Barrier Disruption ◽

Brilliant Blue Fcf ◽

Summary Statement

AbstractUnder conditions of stress, many animals suffer from epithelial barrier disruption that can cause molecules to leak down their concentration gradients, potentially causing a loss of organismal homeostasis, further injury or death. Drosophila is a common insect model, used to study barrier disruption related to aging, traumatic injury, or environmental stress. Net leak of a non-toxic dye (Brilliant blue FCF) from the gut lumen to the hemolymph is often used to identify barrier failure under these conditions, but Drosophila are capable of actively transporting structurally-similar compounds. Here, we examined whether cold stress (like other stresses) causes Brilliant blue FCF (BB-FCF) to appear in the hemolymph of flies fed the dye, and if so whether Drosophila are capable of clearing this dye from their body following chilling. Using in situ midgut leak and transport assays as well as Ramsay assays of Malpighian tubule transport, we tested whether these ionoregulatory epithelia can actively transport BB-FCF. In doing so, we found that the Drosophila midgut and Malpighian tubules can mobilize BB-FCF via an active transcellular pathway, suggesting that elevated concentrations of the dye in the hemolymph may occur from increased paracellular permeability, reduced transcellular clearance, or both.Summary StatementDrosophila are able to actively secrete Brilliant blue FCF, a commonly used marker of barrier dysfunction

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

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.184 ◽

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.

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Eicosapentaenoic Acid, Persantine, and Aspirin for the Prevention of Vein Graft Intimal Hyperplasia

Coronary Artery Surgery in the Nineties ◽

10.1007/978-3-642-45622-0_35 ◽

1987 ◽

pp. 179-179

Author(s):

R. W. Landymore ◽

M. A. MacAulay ◽

B. Sheridan ◽

C. Cameron

Keyword(s):

Eicosapentaenoic Acid ◽

Intimal Hyperplasia ◽

Vein Graft

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

Circulation ◽

10.1161/circ.130.suppl_2.15922 ◽

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.

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