Techniques to Preserve Endothelial Cells in Vein Grafts: History
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Subjects: Surgery | Cardiac & Cardiovascular Systems | Cell Biology
Contributor:
Liam W. McQueen
,
Shameem S. Ladak
,
Georgia R. Layton
,
Hardeep Aujla
,
Adewale Adebayo
,
Mustafa Zakkar

Endothelial cells comprise the intimal layer of the vasculature, playing a crucial role in facilitating and regulating aspects such nutrient transport, vascular homeostasis, and inflammatory response. Endothelial dysfunction is believed to be a key driver for vein graft disease—a pathology in which vein grafts utilised in coronary artery bypass graft surgery develop intimal hyperplasia and accelerated atherosclerosis, resulting in poor long-term patency rates. Activation and denudation of the endothelium following surgical trauma and implantation of the graft encourage a host of immune, inflammatory, and cellular differentiation responses that risk driving the graft to failure. Several approaches have been developed to mitigate the onset and progression of this pathology both clincally and surgically, including optimisation of surgical technique, vein preservation conditions and pharma-modulation. Novel approaches are also under investigation in recent years, including the use of topical gene therapy and the utilisation of endothelial progenitor/colony-forming cells to regenerate vein grafts with the view to improving patient outcomes.

  • endothelial dysfunction
  • vein graft disease
  • intimal hyperplasia

1. Harvesting Techniques

The conventional technique (CT) for vein harvest as initially described by Favaloro et al. [1] entails vein exposure along its length through a longitudinal incision following the contours of the leg and is then harvested in a skeletonised fashion, stripped of surrounding peri-vascular tissue. This induces a degree of venospasm that is subsequently counteracted with manual distention of the vein using crystalloid or blood solutions. Moreover, inflating the vein during the harvest to check for side branches at pressures significantly greater than that of the human vascular system disrupts the endothelium [2], promotes thrombosis [3] and damages the tunica within the vein wall [4]. Damage to the endothelium alters the release of endothelial-derived vasoactive substances including NO, prostanoids, and endothelin-1. In response to damage, the EC production of NO and prostacyclin is reduced but production of prothrombotic factors such as thromboxane and endothelin-1 is increased [5]. Damaged endothelium is pro-coagulant and acute thrombosis is a primary cause of early graft failure [6].
The no-touch technique (NTT) was first described by de Souza in 1996 [7]. Souza proposed that the vein could be harvested with surrounding adventitia, and by doing so, the vein is cushioned by a border of soft tissue which contains the important perivascular structures such as vasa vasorum (VV) and nerves. Importantly, the vein is not directly handled during this process. This technique preserves both the endothelium of the vessel and the microvasculature that nourishes the vein wall. The VV has been shown to maintain perfusion of the vein wall through direct contact with the vein lumen after harvest [8] and demonstrate much greater intimal density and penetration compared to arterial grafts, suggesting a greater significance in the maintenance of luminal viability after harvest. Stripping of the VV by CT therefore promotes ischaemia within the LSV wall with a subsequent detrimental impact on patency, [9] which is likely of larger impact than the associated ischaemia of arteries harvested by CT. The NTT therefore avoids physical disruption to these surrounding tissues, limiting ischaemic injury to the endothelium and provides a physical buffer to limit inadvertent kinking of the graft.
Most of the surrounding ‘cushion’ with which the vein is harvested is composed of fat. Lipocytes have been demonstrated to be a vital source of locally derived vasoactive factors essential for the regulation of vascular tone [10], especially NO. There is compelling evidence that NO expression in vein grafts after CABG plays a key role in the reduction of both IH and atherosclerosis in mouse models [11]. Dashwood et al. [12] demonstrated the presence of eNOS and NO within the periadventitial fat surrounding the LSV following harvest using NTT. This suggests that another benefit of the NTT is not only avoidance of direct physical insults, but also by preservation of the vasoactive sources local to the vein. A further benefit of the NTT relates to the minimised distention of the vein during preparation, which is known to impact on EC integrity, and was previously demonstrated by Angelini et al. [4][13] who confirmed previously that elevated distention pressure causes a reduction in the concentration of adenosine triphosphate (ATP) within the vein and that preservation fluids have the potential to improve ATP levels. The superiority of the NTT was more recently confirmed clinically with higher patency rates of veins harvested by this method as compared to radial arteries or veins harvested conventionally. Furthermore, this also appears to translate into better outcomes as demonstrated by Tian et al. [14] in their multicentre randomised control trial of 2533 patients. It is essential to note that the NTT is more challenging in patients who are obese and when the LSV is very superficial due to anatomical variation [7].

2. Storage Conditions

Once harvested, the LSV is stored in a preservation solution of the surgeon’s choice whilst the heart is prepared for grafting. The solution of choice is a spectrum of crystalloid to autologous blood solutions with various additives intended to buffer pH, confer osmotic impact, act as antioxidants, and mimic the normal composition of bodily intracellular fluid. During this time spent following harvest and prior to implantation, the LSV is in a period of relative ischaemia. The role of preservation fluids is therefore to attenuate EC damage where possible [15]. The primary source of ATP within the LSV is SMCs within the vein media and so the metabolic function of SMCs can be considered by the available concentration of ATP. Heparinised autologous whole blood (AWB) has been shown to better preserve ATP levels compared to normal saline. In fact, AWB has been shown in several studies to improve the vascular contractile reserve and EC function compared to normal saline [15][16][17] through maintenance of SMC tone and integral EC functions such as vasoactivity and platelet activation. Whilst heparin itself exhibits toxicity to the endothelium [18], the addition of whole blood appears to be protective which may be a consequence of its natural contents of energy sources, pH buffers, free-radical scavengers [16].
Papaverine is a commonly evaluated component of preservation fluid to induce SMC relaxation [19]. It is suggested that it may cause chemical damage to the endothelium due to its acidic pH and may also reduce local prostacyclin production. However, it has been demonstrated to reduce venospasm and EC preservation compared to AWB or isotonic crystalloids alone. The vein wall reacts to most local stimuli by undergoing prolonged muscular contraction, which disrupts the endothelium by reducing luminal surface area and causing herniation of SMCs into the lumen which, in turn, denudates the EC layer [20]. Increased SMC relaxation by vasodilators such as papaverine therefore mitigates venospasm, allowing the use of lower distention pressures during harvesting, thereby attenuating loss of ECs and EC damage.
More recently, new solutions have come to market. DuraGraft® (Somahlution, Jupiter, FL, USA) is marketed as a one-time intraoperative treatment for the purposes of reducing vascular EC damage. It is a physiological salt solution (PSS) with additives to attenuate ischaemia and reperfusion injury [21]. Although, theoretically, solutions like these can make a difference, there is very limited data available to compare the efficacy of such solutions. A prospective ex vivo analysis [22] of 26 LSV segments (2 per patient) of which half (n = 13) had been preserved with DuraGraft® and the other half with heparinised Ringer’s lactate for ≥90 min. Veins treated with DuraGraft® demonstrated greater CD31 staining (p < 0.05) and reduced intimal swelling. There was also greater cell viability as demonstrated by Ki67 staining (p < 0.01) and analysis of cell death and senescence marker γH2AX demonstrated reduced numbers of arrested cells or cells with DNA damage in the EC layer of the DuraGraft® group (p < 0.05). Furthermore, using phosphorylated-p53 as a marker of apoptosis, there was a significant reduction of cell death in veins treated with DuraGraft® compared to Ringer’s lactate. Features of hypoxic stress were identified more frequently in non-DuraGraft® treated conduits, although there was no clear reduction of ROS in this group. This study suggests that DuraGraft® attenuates hypoxic injury and better preserves endothelium compared to Ringer’s lactate. Additionally, a comparison of PPS, AWB and DuraGraft® to evaluate endothelial integrity of venous segments was undertaken by Toto et al. [23], which identified a statistically significant reduction in apoptotic cells in the DuraGraft® storage sample after 2 h incubation versus PPS, with apoptotic cells identified using DNA fragmentation detection with fluorescein-12-dUTP. A further evaluation of DuraGraft® by Tekin et al. [24] showed significantly lower total oxidative status (i.e., total oxidant molecules present) for DuraGraft® stored samples, compared to both saline and AWB (p < 0.0001). The total antioxidant status (i.e., the ability to neutralise ROS) was lowest in the saline group and equal between both AWB and DuraGraft®. Combined, these findings suggest that the veins stored in DuraGraft® had higher capacity to combat oxidative stress from ischaemia and therefore better protect EC function.

3. Pharma-Modulation

Pharmacological intervention plays a key role in secondary prevention of vein graft failure. Antiplatelet therapy has played a crucial role in improving outcomes after CABG and reducing vein graft failure, with administration of antiplatelets such as aspirin frequently utilised in clinical practice to mitigate complications following surgery [25].

3.1. Aspirin

The long-term benefit of aspirin after CABG is mediated through reduction and prevention of platelet aggregation and a resultant reduction of thrombus formation, largely mediated by a reduction of thromboxane A2 (TXA2). Beyond platelet inhibition, aspirin also has a significant role in upregulation of EC NO synthesis [26]. The beneficial cardiovascular effects of aspirin are mediated through its inhibition of cyclooxygenase–1 (COX-1) activity. COX-1 is expressed within ECs and is responsible for the production of prostaglandins and resultant production of prostanoids such as TXA2. TXA2 stimulates platelet aggregation and the release of vasoactive pro-coagulant and pro-inflammatory factors; thus, many of the favourable effects of aspirin are attributed to the inhibition of TXA2. TXA2 has been shown to interfere with key endothelium-dependent pathways responsible for regulating blood flow via modulation of calcium activated potassium channels and impairment of cell signalling between EC and SMC layers, thereby impairing EC dependent vasodilation [27]. Aspirin has also been shown to evoke activation of eNOS and therefore increase NO synthesis. This occurs not only within ECs but within platelets themselves and appears to be independent of both COX-1 inhibition and TXA2 production. Two randomised studies have shown a significant increase in markers of NO formation (i.e., HO-1 and ADMA) in a non-dose-dependent fashion in patients with cardiovascular disease, supporting the hypothesis that an aspirin-mediated benefit occurs through the formation of NO, not just the commonly reported mechanism of platelet inhibition [28][29].

3.2. Statins

Statins are predominantly utilised for their lipid-lowering properties. However, when given perioperatively to patients undergoing CABG, they have been shown to improve EC function, maintain NO levels and promote antioxidant activity, as well as inhibiting vasoconstriction, thrombosis, and the inflammatory response. Yang et al. [30] were able to demonstrate direct enhancement of saphenous vein EC expression of eNOS and subsequent increased NO production from ECs in response to statin therapy. A reduction in low-density lipoprotein (LDL) cholesterol has also been shown to result in reversal of EC impairment [31]. The clinical associations have also been proven—one of the first studies to randomise patients to statins after CABG was able to demonstrate that aggressive statin treatment (40 mg/day) after CABG was associated with less angiographic evidence of vein graft occlusion. Specifically, they identified an average of 10% increased vessel occlusion in patients undergoing aggressive statin therapy versus 21% increased occlusion in patients undergoing moderate (2.5 mg/day) statin therapy (p < 0.0001), as well as a reduced mean number of grafts exhibiting progression of atherosclerosis (25% in the aggressive treated group versus 39% in the moderate treated group, p < 0.001) [32].

3.3. ACE Inhibitors/AngII Receptor Antagonists

Angiotensin-converting enzyme (ACE) is a key regulator of the renin angiotensin aldosterone system. Renin, which is synthesised as an inactive pre-pro-hormone, undergoes a proteolytic cascade resulting in its release into the system circulation as its active form. Within the circulation it acts upon angiotensinogen to generate angiotensin-I (AngI). AngI is subsequently cleaved by ACE to produce AngII. AngII is the primary atherogenic effector of the renin angiotensin aldosterone system, and activation of this system is associated with increased atherothrombotic events [33].
Many in vitro and in vivo animal studies have implicated AngII within pathways known to contribute to vein graft disease. AngII has been found to promote IH [34] and both SMC hypertrophy [35] and proliferation [36][37], and is evidenced to activate key inflammatory pathways which precipitate vein graft disease. Specifically, AngII has been demonstrated to stimulate release of IL6 from SMCs and macrophages [38] and to activate nicotinamide dinucleotide phosphatase oxidase with resultant production of ROS [39][40], thereby promoting oxidative stress within the vascular microenvironment. Angiotensin-converting-enzyme inhibitor (ACEi), Ramipril, assists in the preservation of EC function by inhibiting AngII production and attenuating the aforementioned pathways promoting inflammation and oxidative stress [41]. They also enhance NO production through prolongation of the half-life of bradykinin and stabilisation of the bradykinin receptor linked to the formation of NO [42]. Similarly, AngII type-1 receptor antagonists (ARBs) (i.e., losartan) exert similar benefit through competitive inhibition of AngII via its receptor.
Several human studies have evidenced improved arterial EC function following the administration of ACEi and ARBs in patients with diabetes [43] and hypercholesterolaemia [44]. Several large randomised studies including QUO VADIS [45] and IMAGINE [46] have looked at their clinical benefit after CABG but did not assess features of EC damage or post-operative vein graft patency directly. A 2005 blinded, randomised trial by Trevelyan et al. [47] demonstrated improvement in systemic endothelial function following pre-operative patient treatment with both ACEi (enalapril) or ARB (losartan). EC function, quantified by endothelial dependent flow mediated dilatation (FMD) of the brachial artery, increased from baseline in all groups (5.2% in surgery and enalapril group, p = 0.015 versus 5.0% in surgery and losartan group p = 0.0004 versus 3.0% in surgery alone group p = 0.05) at three months after CABG and was sustained at five months post-operatively. Interestingly all patients, even those who did not receive any pharma-modulation, demonstrated improved systemic endothelial function after CABG suggesting that coronary revascularisation alone confers some improvement of endothelial function.
Furthermore, research into lectin-like oxidised-LDL receptor-1 (LOX-1) has been shown to increase in response to ox-LDL and specifically in atherosclerotic plaques (such as those found in vein graft disease) [48][49][50]. These receptors have also been shown to upregulate in response to AngII through activation of AngII type-1 receptors, and interestingly the use of the ARB losartan inhibits LOX-1 upregulation [51][52][53]. Work by Ge et al. [54] utilising rabbit models identified that losartan treatment attenuated lesions and improved plaque stability; however, no reduction in intimal area was observed compared to the untreated group. LOX-1 expression was shown to increase in both the endothelium and lesion area of control mice, which appeared to be attenuated upon losartan treatment, suggesting that LOX-1 downregulation may confer benefits in the attenuation of vein graft disease.

4. Novel Approaches to Endothelial Preservation

Beyond the aforementioned approaches to endothelial preservation, several novel approaches are being considered including, but not limited to, gene therapy and utilisation of endothelial progenitor/colony-forming cells (EPCs/ECFCs).
Many of the most recent advances in gene therapy relating to vein graft disease have been reviewed in detail by Southerland et al. [55]. In brief, vein graft disease presents as a strong candidate for this treatment approach, predominantly due to the ability to administer the therapy ex vivo prior to reimplantation into the arterial circulation. This approach has the effect of ensuring localised delivery of the therapeutic whilst mitigating the effects of off-target or systemic effects.
There have been a significant number of pre-clinical studies undertaken to investigate the feasibility of gene therapy, with the primary targets relating to endothelial and smooth muscle cell preservation, and mitigation of thrombosis and inflammation. Approaches have included intraluminal or pressure-mediated transfection to induce eNOS overexpression [55][56], COX-1 overexpression [57][58], thrombomodulin and tPA overexpression [59][60], MCP1 inhibition [61][62], NF-κB inhibition [63][64], and E2F inhibition [65] among others. Of note, the E2F inhibition approach via oligodeoxynucleotide delivery had been expanded to human subjects (PREVENT trial) following success in pre-clinical models; however, outcomes of phase 3 have not shown significant differences in graft stenosis or patency by 12 months.
As an alternative approach, researchers are also investigating the potential of endothelial progenitor/colony-forming cells as a means of facilitating re-re-endothelialisation of saphenous vein grafts following implantation, with much of this branch of research having been concisely summarised by Paschalaki et al. [66]. In brief, EPCs categorise numerous populations of cells which express markers endothelial-specific markers which are known to contribute to vascularisation. ECFCs, as a subset, have been identified as having characteristics specific to endothelial origins, and these cells have been investigated in relation to a substantial number of vascular diseases, and have been considered in clinical applications such as gene therapy, vessel/tissue bioengineering, endothelial preservation, and repair.
With specific consideration of vein graft disease, circulating EPCs have been shown to regenerate graft endothelium in mice models, with approximately one-third of regenerated ECs derived from this circulating, bone-marrow derived population [67]. Furthermore, phenotypic analysis of peripheral blood derived ECFCs, compared to both human-derived arterial and venous ECs under high pulsatile flow conditions, depicted a highly proliferative, adaptable cell population which conforms to hemodynamic conditions, adopting a phenotype resembling that of the arterial ECs [68]. Interestingly, a study conducted by Feng et al. [69] was able to identify a therapeutic approach to increasing incorporation of ECFCs into vein graft endothelium through the topical treatment of high-density lipoprotein to the vessel adventitia. This treatment approach in mice showed a significant reduction in neointimal area (p < 0.001), improved blood flow (p < 0.0001), reduced inflammatory response (p < 0.05) determined by leukocyte adhesion, and enhanced endothelial regeneration (p < 0.05). This regeneration was attributed to improved ECFC migration and adhesion, which appear dependent on scavenger receptor class B type 1 expression, extracellular signal-regulated kinases and NO signalling.
Another study of note utilised human umbilical cord blood endothelial progenitor cells as a means of facilitating re-endothelialisation of vein grafts [70]. This group were able to identify that these cells exhibit superior adhesion capacity to cultured SMCs under shear stress conditions (0.5 dyne/cm2) compared to arterial ECs and peripheral blood ECs, believed to be the result of increased expression of cell surface α5β1 integrin. The proliferative capacity of these cells, to facilitate potential re-endothelialisation was also shown to be significantly faster under both shear conditions (0–15 dynes/cm2) and compared to arterial and peripheral blood ECs. Finally, using an immunodeficient vein graft mouse model, the group identified, with results indicating that these progenitor cells were capable of accelerating graft re-endothelialisation and, consequently, mitigating graft thrombosis. Whilst these results are promising, the haemodynamic conditions assessed here are significantly lower than those of the in situ arterial environment, and the highly thrombotic mouse model likely overestimates the anti-thrombotic nature of these cells. However, despite these drawbacks, EPCs present as a novel therapeutic approach to the preservation of endothelial function.

This entry is adapted from the peer-reviewed paper 10.3390/cells11193066

References

  1. Rene G. Favaloro; Saphenous vein graft in the surgical treatment of coronary artery disease. The Journal of Thoracic and Cardiovascular Surgery 1969, 58, 178-185, 10.1016/s0022-5223(19)42599-3.
  2. David Dries; S.Fazal Mohammad; Stephen C. Woodward; Russell M. Nelson; P.Scott Johnston; The influence of harvesting technique on endothelial preservation in saphenous veins. Journal of Surgical Research 1992, 52, 219-225, 10.1016/0022-4804(92)90077-d.
  3. Richard P. Cambria; Joseph Megerman; William M. Abbott; Endothelial Preservation in Reversed and In Situ Autogenous Vein Grafts. Annals of Surgery 1985, 202, 50-55, 10.1097/00000658-198507000-00007.
  4. Gianni D Angelini; Stefano L Passani; Iain M Breckenridge; Andrew C Newby; Nature and pressure dependence of damage induced by distension of human saphenous vein coronary artery bypass grafts. Cardiovascular Research 1987, 21, 902-907, 10.1093/cvr/21.12.902.
  5. Gokce Topal; Andrzej Loesch; Michael R. Dashwood; COVID-19 — Endothelial Axis and Coronary Artery Bypass Graft Patency: a Target for Therapeutic Intervention?. Brazilian Journal of Cardiovascular Surgery 2020, 35, 757-763, 10.21470/1678-9741-2020-0303.
  6. Margreet R. De Vries; Karin H. Simons; J. Wouter Jukema; Jerry Braun; Paul Quax; Vein graft failure: from pathophysiology to clinical outcomes. Nature Reviews Cardiology 2016, 13, 451-470, 10.1038/nrcardio.2016.76.
  7. Domingos Souza; A New No-Touch Preparation Technique:Technical notes. Scandinavian Journal of Thoracic and Cardiovascular Surgery 1996, 30, 41-44, 10.3109/14017439609107239.
  8. Mats Dreifaldt; Domingos S.R. Souza; Andrzej Loesch; John R. Muddle; Mats G Karlsson; Derek Filbey; Lennart Bodin; Lars Norgren; Michael R. Dashwood; The “no-touch” harvesting technique for vein grafts in coronary artery bypass surgery preserves an intact vasa vasorum. The Journal of Thoracic and Cardiovascular Surgery 2011, 141, 145-150, 10.1016/j.jtcvs.2010.02.005.
  9. Andrzej Loesch; Michael R. Dashwood; Vasa vasorum inside out/outside in communication: a potential role in the patency of saphenous vein coronary artery bypass grafts. Journal of Cell Communication and Signaling 2018, 12, 631-643, 10.1007/s12079-018-0483-1.
  10. Maik Gollasch; Galyna Dubrovska; Paracrine role for periadventitial adipose tissue in the regulation of arterial tone. Trends in Pharmacological Sciences 2004, 25, 647-653, 10.1016/j.tips.2004.10.005.
  11. Michael R Dashwood; Andrzej Loesch; Inducible nitric oxide synthase and vein graft performance in patients undergoing coronary artery bypass surgery: physiological or pathophysiological role?. Current Vascular Pharmacology 2014, 12, 144-151, 10.2174/157016111201140327164409.
  12. Michael R. Dashwood; Audrey Dooley; Xu Shi-Wen; David J. Abraham; Domingos S.R. Souza; Does Periadventitial Fat-Derived Nitric Oxide Play a Role in Improved Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Surgery?. Journal of Vascular Research 2007, 44, 175-181, 10.1159/000099833.
  13. G D Angelini; Iain M Breckenridge; Eric G Butchart; Stephen H Armistead; Kate M Middleton; Andrew H Henderson; Andrew C Newby; Metabolic damage to human saphenous vein during preparation for coronary artery bypass grafting. Cardiovascular Research 1985, 19, 326-334, 10.1093/cvr/19.6.326.
  14. Meice Tian; Xianqiang Wang; Hansong Sun; Wei Feng; Yunhu Song; Feng Lu; Liqing Wang; Yang Wang; Bo Xu; Huaibin Wang; et al. No-Touch Versus Conventional Vein Harvesting Techniques at 12 Months After Coronary Artery Bypass Grafting Surgery: Multicenter Randomized, Controlled Trial. Circulation 2021, 144, 1120-1129, 10.1161/circulationaha.121.055525.
  15. Ismail Bouhout; Walid Ben Ali; Louis Paul Perrault; The effect of storage solutions on endothelial function and saphenous vein graft patency. Indian Journal of Thoracic and Cardiovascular Surgery 2018, 34, 258-265, 10.1007/s12055-018-0720-5.
  16. Manuel Wilbring; Annette Ebner; Katrin Schoenemann; Michael Knaut; Sems Malte Tugtekin; Birgit Zatschler; Thomas Waldow; Konstantin Alexiou; Klaus Matschke; Andreas Deussen; et al. Heparinized blood better preserves cellular energy charge and vascular functions of intraoperatively stored saphenous vein grafts in comparison to isotonic sodium-chloride-solution. Clinical Hemorheology and Microcirculation 2013, 55, 445-455, 10.3233/CH-131781.
  17. G M Lawrie; D E Weilbacher; P D Henry; Endothelium-dependent relaxation in human saphenous vein grafts. Effects of preparation and clinicopathologic correlations.. The Journal of Thoracic and Cardiovascular Surgery 1990, 100, 612-20, .
  18. S Carpentier; M Murawsky; A Carpentier; Cytotoxicity of cardioplegic solutions: evaluation by tissue culture.. Circulation 1981, 64, II90-95, .
  19. Katsunori Takeuchi; Shigeru Sakamoto; Yasuhiro Nagayoshi; Hisateru Nishizawa; Junichi Matsubara; Reactivity of the human internal thoracic artery to vasodilators in coronary artery bypass grafting. European Journal of Cardio-Thoracic Surgery 2004, 26, 956-959, 10.1016/j.ejcts.2004.07.047.
  20. F. Gregory Baumann; Frank P. Catinella; Joseph N. Cunningham; Frank C. Spencer; Vein Contraction and Smooth Muscle Cell Extensions as Causes of Endothelial Damage during Graft Preparation. Annals of Surgery 1981, 194, 199-211, 10.1097/00000658-198108000-00015.
  21. DuraGraft for preserving vascular grafts . NICE. Retrieved 2022-10-10
  22. Thomas Aschacher; Ulrike Baranyi; Olivia Aschacher; Eva Eichmair; Barbara Messner; Daniel Zimpfer; Roxana Moayedifar; Guenther Laufer; Maximilian Y. Emmert; Sigrid E. Sandner; et al. A Novel Endothelial Damage Inhibitor Reduces Oxidative Stress and Improves Cellular Integrity in Radial Artery Grafts for Coronary Artery Bypass. Frontiers in Cardiovascular Medicine 2021, 8, ., 10.3389/fcvm.2021.736503.
  23. Francesca Toto; Tiziano Torre; Lucia Turchetto; Viviana Lo Cicero; Sabrina Soncin; Catherine Klersy; Stefanos Demertzis; Enrico Ferrari; Efficacy of Intraoperative Vein Graft Storage Solutions in Preserving Endothelial Cell Integrity during Coronary Artery Bypass Surgery. Journal of Clinical Medicine 2022, 11, 1093, 10.3390/jcm11041093.
  24. Ilker Tekin; Meltem Demir; Sebahat Özdem; Effect of different storage solutions on oxidative stress in human saphenous vein grafts. Journal of Cardiothoracic Surgery 2022, 17, 1-6, 10.1186/s13019-022-01752-7.
  25. Alexander Kulik; Marc Ruel; Hani Jneid; T. Bruce Ferguson; Loren F. Hiratzka; John S. Ikonomidis; Francisco Lopez-Jimenez; Sheila M. McNallan; Mahesh Patel; Véronique L. Roger; et al. Secondary Prevention After Coronary Artery Bypass Graft Surgery. Circulation 2015, 131, 927-964, 10.1161/cir.0000000000000182.
  26. V Fuster; M L Dyken; P S Vokonas; C Hennekens; Aspirin as a therapeutic agent in cardiovascular disease. Special Writing Group.. Circulation 1993, 87, 659-675, 10.1161/01.cir.87.2.659.
  27. David C. Ellinsworth; Nilima Shukla; Ingrid Fleming; Jamie Y. Jeremy; Interactions between thromboxane A2, thromboxane/prostaglandin (TP) receptors, and endothelium-derived hyperpolarization. Cardiovascular Research 2014, 102, 9-16, 10.1093/cvr/cvu015.
  28. Charles H. Hennekens; Wendy R. Schneider; Alex Pokov; Scott Hetzel; David DeMets; Victor Serebruany; Henning Schröder; A Randomized Trial of Aspirin at Clinically Relevant Doses and Nitric Oxide Formation in Humans. Journal of Cardiovascular Pharmacology and Therapeutics 2010, 15, 344-348, 10.1177/1074248410375091.
  29. Scott Hetzel; David DeMets; Ricky Schneider; Steven Borzak; Wendy Schneider; Victor Serebruany; Henning Schröder; Charles H. Hennekens; Aspirin Increases Nitric Oxide Formation in Chronic Stable Coronary Disease. Journal of Cardiovascular Pharmacology and Therapeutics 2013, 18, 217-221, 10.1177/1074248413482753.
  30. Zhihong Yang; Toshiyoki Kozai; Bernd van de Loo; Hema Viswambharan; Mario Lachat; Marko I Turina; Tadeusz Malinski; Thomas F Lüscher; HMG-CoA reductase inhibition improves endothelial cell function and inhibits smooth muscle cell proliferation in human saphenous veins. Journal of the American College of Cardiology 2000, 36, 1691-1697, 10.1016/s0735-1097(00)00924-4.
  31. Todd J. Anderson; Ian T. Meredith; Alan C. Yeung; Balz Frei; Andrew P. Selwyn; Peter Ganz; The Effect of Cholesterol-Lowering and Antioxidant Therapy on Endothelium-Dependent Coronary Vasomotion. New England Journal of Medicine 1995, 332, 488-493, 10.1056/nejm199502233320802.
  32. post coronary artery bypass graft trial investigators; The Effect of Aggressive Lowering of Low-Density Lipoprotein Cholesterol Levels and Low-Dose Anticoagulation on Obstructive Changes in Saphenous-Vein Coronary-Artery Bypass Grafts. New England Journal of Medicine 1997, 336, 153-163, 10.1056/nejm199701163360301.
  33. Michael H. Alderman; Shantha Madhavan; Wee L. Ooi; Hillel Cohen; Jean E. Sealey; John H. Laragh; Association of the Renin-Sodium Profile with the Risk of Myocardial Infarction in Patients with Hypertension. New England Journal of Medicine 1991, 324, 1098-1104, 10.1056/nejm199104183241605.
  34. Martin K. Oʼdonohoe; Lewis B. Schwartz; Zeljko S. Radio; Eileen M. Mikat; Richard L. McCANN; Per-Otto Hagen; Chronic ACE Inhibition Reduces Intimal Hyperplasia in Experimental Vein Grafts. Annals of Surgery 1991, 214, 727-732, 10.1097/00000658-199112000-00014.
  35. A A Geisterfer; M J Peach; G K Owens; Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells.. Circulation Research 1988, 62, 749-756, 10.1161/01.res.62.4.749.
  36. Mark Campbell-Boswell; Abel Lazzarini Robertson; Effects of angiotensin II and vasopressin on human smooth muscle cells in vitro. Experimental and Molecular Pathology 1981, 35, 265-276, 10.1016/0014-4800(81)90066-6.
  37. M J Daemen; D M Lombardi; F T Bosman; S M Schwartz; Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall.. Circulation Research 1991, 68, 450-456, 10.1161/01.res.68.2.450.
  38. Bernhard Schieffer; Elisabeth Schieffer; Denise Hilfiker-Kleiner; Andres Hilfiker; Petri T. Kovanen; Maija Kaartinen; Jörg Nussberger; Wolfgang Harringer; Helmut Drexler; Expression of Angiotensin II and Interleukin 6 in Human Coronary Atherosclerotic Plaques. Circulation 2000, 101, 1372-1378, 10.1161/01.cir.101.12.1372.
  39. K K Griendling; C A Minieri; J D Ollerenshaw; R W Alexander; Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.. Circulation Research 1994, 74, 1141-1148, 10.1161/01.res.74.6.1141.
  40. Hirofumi Hitomi; Toshiki Fukui; Kumiko Moriwaki; Keisuke Matsubara; Guang-Ping Sun; Matlubur Rahman; Akira Nishiyama; Hideyasu Kiyomoto; Shoji Kimura; Koji Ohmori; et al. Synergistic effect of mechanical stretch and angiotensin II on superoxide production via NADPH oxidase in vascular smooth muscle cells. Journal of Hypertension 2006, 24, 1089-1095, 10.1097/01.hjh.0000226199.51805.88.
  41. Jian-Zhong Sun; Long-Hui Cao; Hong Liu; ACE inhibitors in cardiac surgery: current studies and controversies. Hypertension Research 2010, 34, 15-22, 10.1038/hr.2010.188.
  42. F. Enseleit; F. Ruschitzka; T.F. Lüscher; Angiotensin-converting enzyme inhibition and endothelial dysfunction: focus on ramipril. European Heart Journal Supplements 2003, 5, A31-A36, 10.1016/S1520-765X(03)90061-7.
  43. Gerard O’Driscoll; Daniel Green; Andrew Maiorana; Kim Stanton; Frances Colreavy; Roger Taylor; Improvement in endothelial function by angiotensin-converting enzyme inhibition in non–insulin-dependent diabetes mellitus. Journal of the American College of Cardiology 1999, 33, 1506-1511, 10.1016/s0735-1097(99)00065-0.
  44. A F Lee; J B Dick; C E Bonnar; A D Struthers; Lisinopril improves arterial function in hyperlipidaemia.. Clinical Science 1999, 96, 441-448, .
  45. Margaretha Oosterga; Adriaan A Voors; Yigal M Pinto; Hendrik Buikema; Jan G Grandjean; J.Herre Kingma; Harry J.G.M Crijns; Wiek H van Gilst; Effects of quinapril on clinical outcome after coronary artery bypass grafting (the QUO VADIS study). The American Journal of Cardiology 2001, 87, 542-546, 10.1016/s0002-9149(00)01428-4.
  46. Jean L. Rouleau; Wayne J. Warnica; Richard Baillot; Pierre J. Block; Sidney Chocron; David Johnstone; Martin G. Myers; Cristina-Dana Calciu; Sonia Dalle-Ave; Pierre Martineau; et al. Effects of Angiotensin-Converting Enzyme Inhibition in Low-Risk Patients Early After Coronary Artery Bypass Surgery. Circulation 2008, 117, 24-31, 10.1161/circulationaha.106.685073.
  47. J Trevelyan; E W A Needham; A Morris; R K Mattu; Comparison of the effect of enalapril and losartan in conjunction with surgical coronary revascularisation versus revascularisation alone on systemic endothelial function. Heart 2005, 91, 1053-1057, 10.1136/hrt.2004.036897.
  48. Tatsuya Sawamura; Noriaki Kume; Takuma Aoyama; Hideaki Moriwaki; Hajime Hoshikawa; Yuichi Aiba; Takeshi Tanaka; Soichi Miwa; Yoshimoto Katsura; Toru Kita; et al. An endothelial receptor for oxidized low-density lipoprotein. Nature 1997, 386, 73-77, 10.1038/386073a0.
  49. J.L. Mehta; D.Y. Li; Identification and Autoregulation of Receptor for OX-LDL in Cultured Human Coronary Artery Endothelial Cells. Biochemical and Biophysical Research Communications 1998, 248, 511-514, 10.1006/bbrc.1998.9004.
  50. Hiroharu Kataoka; Noriaki Kume; Susumu Miyamoto; Manabu Minami; Hideaki Moriwaki; Takatoshi Murase; Tatsuya Sawamura; Tomoh Masaki; Nobuo Hashimoto; Toru Kita; et al. Expression of Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 in Human Atherosclerotic Lesions. Circulation 1999, 99, 3110-3117, 10.1161/01.cir.99.24.3110.
  51. D. Y. Li; Y. C. Zhang; M. I. Philips; T. Sawamura; J. L. Mehta; Upregulation of Endothelial Receptor for Oxidized Low-Density Lipoprotein (LOX-1) in Cultured Human Coronary Artery Endothelial Cells by Angiotensin II Type 1 Receptor Activation. Circulation Research 1999, 84, 1043-1049, 10.1161/01.res.84.9.1043.
  52. Henning Morawietz; Uwe Rueckschloss; Bernd Niemann; Nicole Duerrschmidt; Jan Galle; Kavous Hakim; Hans-Reinhard Zerkowski; Tatsuya Sawamura; Juergen Holtz; Angiotensin II Induces LOX-1, the Human Endothelial Receptor for Oxidized Low-Density Lipoprotein. Circulation 1999, 100, 899-902, 10.1161/01.cir.100.9.899.
  53. Hongjiang Chen; Dayuan Li; Tatsuya Sawamura; Kazuhiko Inoue; Jawahar L. Mehta; Upregulation of LOX-1 Expression in Aorta of Hypercholesterolemic Rabbits: Modulation by Losartan. Biochemical and Biophysical Research Communications 2000, 276, 1100-1104, 10.1006/bbrc.2000.3532.
  54. Junbo Ge; Dong Huang; Chun Liang; Yukun Luo; Qingzhe Jia; Keqiang Wang; Upregulation of lectinlike oxidized low-density lipoprotein receptor-1 expression contributes to the vein graft atherosclerosis: modulation by losartan. Atherosclerosis 2004, 177, 263-268, 10.1016/j.atherosclerosis.2004.07.021.
  55. Kevin W. Southerland; Sarah B. Frazier; Dawn E. Bowles; Carmelo A. Milano; Christopher D. Kontos; Gene therapy for the prevention of vein graft disease. Translational Research 2013, 161, 321-338, 10.1016/j.trsl.2012.12.003.
  56. Shinji Ohta; Kimihiro Komori; Yoshikazu Yonemitsu; Toshihiro Onohara; Takuya Matsumoto; Keizo Sugimachi; Intraluminal gene transfer of endothelial cell-nitric oxide synthase suppresses intimal hyperplasia of vein grafts in cholesterol-fed rabbit: A limited biological effect as a result of the loss of medial smooth muscle cells. Surgery 2002, 131, 644-653, 10.1067/msy.2002.124878.
  57. Harald C. Eichstaedt; Qi Liu; Zhiqiang Chen; George C. Bobustuc; Toya Terry; James T. Willerson; Pierre Zoldhelyi; Gene Transfer of COX-1 Improves Lumen Size and Blood Flow in Carotid Bypass Grafts. Journal of Surgical Research 2010, 161, 162-167, 10.1016/j.jss.2008.12.012.
  58. Pierre Zoldhelyi; Janice McNatt; Xiao-Ming Xu; David Loose-Mitchell; Robert S. Meidell; Fred J. ClubbJr; L. Maximilian Buja; James T. Willerson; Kenneth K. Wu; Prevention of Arterial Thrombosis by Adenovirus-Mediated Transfer of Cyclooxygenase Gene. Circulation 1996, 93, 10-17, 10.1161/01.cir.93.1.10.
  59. Antony Y. Kim; Peter L. Walinsky; Frank D. Kolodgie; Ce Bian; Jason L. Sperry; Clayton B. Deming; Eric A. Peck; Jay G. Shake; Gregory B. Ang; Richard H. Sohn; et al. Early Loss of Thrombomodulin Expression Impairs Vein Graft Thromboresistance. Circulation Research 2002, 90, 205-212, 10.1161/hh0202.105097.
  60. Marcella J. Wyatt; Andrew C. Newby; Anita C. Thomas; Reduction of early vein graft thrombosis by tissue plasminogen activator gene transfer. Thrombosis and Haemostasis 2009, 102, 145-152, 10.1160/th08-11-0772.
  61. A. Schepers; D. Eefting; P.I. Bonta; J.M. Grimbergen; M.R. de Vries; V. van Weel; C.J. de Vries; K. Egashira; J.H. van Bockel; P.H.A. Quax; et al. Anti–MCP-1 Gene Therapy Inhibits Vascular Smooth Muscle Cells Proliferation and Attenuates Vein Graft Thickening Both In Vitro and In Vivo. Arteriosclerosis, Thrombosis, and Vascular Biology 2006, 26, 2063-2069, 10.1161/01.atv.0000235694.69719.e2.
  62. Hideki Tatewaki; Kensuke Egashira; Satoshi Kimura; Takahiro Nishida; Shigeki Morita; Ryuji Tominaga; Blockade of monocyte chemoattractant protein-1 by adenoviral gene transfer inhibits experimental vein graft neointimal formation. Journal of Vascular Surgery 2007, 45, 1236-1243, 10.1016/j.jvs.2007.01.066.
  63. Takuji Shintani; Yoshiki Sawa; Toshiki Takahashi; Goro Matsumiya; Nariaki Matsuura; Yuji Miyamoto; Hikaru Matsuda; Intraoperative transfection of vein grafts with the NFκB decoy in a canine aortocoronary bypass model: a strategy to attenuate intimal hyperplasia. The Annals of Thoracic Surgery 2002, 74, 1132-1137, 10.1016/s0003-4975(02)03921-8.
  64. Takashi Miyake; Motokuni Aoki; Suguru Shiraya; Kazuo Tanemoto; Toshio Ogihara; Yasufumi Kaneda; Ryuichi Morishita; Inhibitory effects of NFκB decoy oligodeoxynucleotides on neointimal hyperplasia in a rabbit vein graft model. Journal of Molecular and Cellular Cardiology 2006, 41, 431-440, 10.1016/j.yjmcc.2006.04.006.
  65. PREVENT IV Investigators; Efficacy and Safety of Edifoligide, an E2F Transcription Factor Decoy, for Prevention of Vein Graft Failure Following Coronary Artery Bypass Graft Surgery. JAMA 2005, 294, 2446-2454, 10.1001/jama.294.19.2446.
  66. Koralia E. Paschalaki; Anna M. Randi; Recent Advances in Endothelial Colony Forming Cells Toward Their Use in Clinical Translation. Frontiers in Medicine 2018, 5, 295, 10.3389/fmed.2018.00295.
  67. Qingbo Xu; Zhongyi Zhang; Fergus Davison; Yanhua Hu; Circulating Progenitor Cells Regenerate Endothelium of Vein Graft Atherosclerosis, Which Is Diminished in ApoE-Deficient Mice. Circulation Research 2003, 93, e76-86, 10.1161/01.res.0000097864.24725.60.
  68. Xenia Kraus; Edda van de Flierdt; Jannis Renzelmann; Stefanie Thoms; Martin Witt; Thomas Scheper; Cornelia Blume; Peripheral blood derived endothelial colony forming cells as suitable cell source for pre-endothelialization of arterial vascular grafts under dynamic flow conditions. Microvascular Research 2022, 143, 104402, 10.1016/j.mvr.2022.104402.
  69. Yingmei Feng; Stephanie C. Gordts; Feng Chen; Yanhua Hu; Eline Van Craeyveld; Frank Jacobs; Vincent Carlier; Yuanbo Feng; Zhiyong Zhang; Qingbo Xu; et al. Topical HDL administration reduces vein graft atherosclerosis in apo E deficient mice. Atherosclerosis 2011, 214, 271-278, 10.1016/j.atherosclerosis.2010.09.024.
  70. Melissa A. Brown; Lisheng Zhang; Vrad W. Levering; Jiao-Hui Wu; Lisa L. Satterwhite; Leigh Brian; Neil J. Freedman; George A. Truskey; Human Umbilical Cord Blood–Derived Endothelial Cells Reendothelialize Vein Grafts and Prevent Thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology 2010, 30, 2150-2155, 10.1161/atvbaha.110.207076.
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