Extracellular signal-regulated kinase inhibition prevents venous adaptive remodeling via regulation of Eph-B4

Vascular ◽  
2021 ◽  
pp. 170853812199985
Author(s):  
Yuanyuan Guo ◽  
Fan Zhu ◽  
Xiong Zhang ◽  
Guangmin Wu ◽  
Pinting Fu ◽  
...  
Keyword(s):  
Western Blotting ◽  
Vein Graft ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Graft Loss ◽  
Elastic Fibers ◽  
Sprague Dawley ◽  
Vein Grafts ◽  
Graft Stenosis

Objectives Vein graft adaptation (VGA) is a process that vein as a vascular graft conduits in arterial reconstructive surgery; VGA can lead to postoperative vein graft stenosis (VGS) and complications after coronary artery bypass graft and other peripheral artery bypass surgeries. VGA is characterized by vein graft loss the venous features without exhibiting arterial features; furthermore, the activation of ERK inhibited the maintenance of venous properties of the vein graft. We hypothesized that ERK inhibition can affect vein VGS through regulating the expression of EphB4. Methods Rat vein transplantation model was established using wild-type and EphB4+/− Sprague-Dawley rats. Hematoxylin-eosin, Masson, Verhoeff, actin staining, and immunohistochemistry were applied to observe the structure of the vein grafts. Vascular smooth muscle cells (VSMCs) were isolated from the vein and vein grafts. Western blotting was used to determine the expression of p-ERK1/2 and EphB4, and immunofluorescence was applied to detect the expression and location of EphB4. Cell wound scratch assay and CCK8 assay were used to determine the migration and proliferation of VSMCs. Real-time polymerase chain reaction was used to determine the mRNA expression of EphB4. Results Western blotting in vein sample and vein graft sample detected p-ERK1/2 and ERK1/2 expression in both EphB4+/+ and EphB4+/− rats. The expression of p-ERK was increased in vein graft compared to vein. Immunofluorescence in VSMCs form EphB4+/+ and EphB4+/− rats detected EphB4 expression in both cells, and the expression of EphB4 was increased in VSMCs form EphB4+/+ rats. SCH772984 reduces the proliferation and migration of VSMCs. Inhibition of ERK suppressed the increase of vein graft wall thickness, and the expression of collagen fibers, elastic fibers, and α-actin was decreased. Vein graft from EphB4+/− rats reduces the expression of EphB4, and SCH772984 suppressed the decrease of EphB4 in vivo. Vein graft from EphB4+/− rats increased the expression of EphB4, and SCH772984 suppressed the increase of EphB4 in vivo. Conclusions The inhibition of ERK1/2 suppressed the process of VGS by decreasing the proliferation of VSMCs. The ERK-inhibitor SCH772984 suppressed the level of VGS by extending the time of EphB4 expression during the process of VGA, thus maintaining the venousization of vein graft. The mechanism may be that the inhibitor SCH772984 suppresses the level of VGS by extending the time of EphB4 expression during the process of VGA. Therefore, our research provides a new target of VGS treatment by inhibiting the expression of ERK1/2 through the process of VGA.

Targeting Smad-Mediated TGFß Pathway in Coronary Artery Bypass Graft

2020 ◽  
pp. 107424842095103
Author(s):  
Marzuq A. Ungogo
Keyword(s):  
Coronary Artery ◽  
Coronary Artery Bypass ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Artery Bypass ◽  
Bypass Graft ◽  
In Vivo Studies ◽  
Vein Grafts

Revascularization surgeries such as coronary artery bypass grafting (CABG) are sometimes necessary to manage coronary heart disease (CHD). However, more than half of these surgeries fail within 10 years due to the development of intimal hyperplasia (IH) among others. The cytokine transforming growth factor-beta (TGFß) and its signaling components have been found to be upregulated in diseased or injured vessels, and to promote IH after grafting. Interventions that globally inhibit TGFß in CABG have yielded contrasting outcomes in in vitro and in vivo studies including clinical trials. With advances in molecular biology, it becomes clear that TGFß exhibits both protective and damaging roles, and only specific components such as some Smad-dependent TGFß signaling mediate vascular IH. The activin receptor-like kinase (ALK)-mediated Smad-dependent TGFß signaling pathways have been found to be activated in human vascular smooth muscle cells (VSMCs) following injury and in hyperplastic preimplantation vein grafts. It appears that focused targeting of TGFß pathway constitutes a promising therapeutic target to improve the outcome of CABG. This study dissects the role of TGFß pathway in CABG failure, with particular emphasis on the therapeutic potentials of specific targeting of Smad-dependent and ALK-mediated signaling.

Perivascular Nitric Oxide Delivery to Saphenous Vein Grafts Prevents Graft Stenosis after Coronary Artery Bypass Grafting: A Novel Sheep Model

Cardiology ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 8-15 ◽  
Author(s):  
Kyomars Abbasi ◽  
Keivan Shalileh ◽  
Maryam Sotudeh Anvari ◽  
Shahram Rabbani ◽  
Abolfazl Mahdanian ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Coronary Artery Bypass Grafting ◽  
Saphenous Vein ◽  
Artery Bypass ◽  
Bypass Grafting ◽  
Sheep Model ◽  
Vein Grafts ◽  
Graft Stenosis ◽  
Nitric Oxide Delivery

scholarly journals Torsion Does Not Affect Early Vein Graft Patency in the Rat Femoral Artery Model

2018 ◽  
Vol 35 (04) ◽  
pp. 299-305
Author(s):  
Amro Harb ◽  
Maxwell Levi ◽  
Akio Kozato ◽  
Yelena Akelina ◽  
Robert Strauch
Keyword(s):  
Vein Graft ◽  
Graft Failure ◽  
Blood Flow Rate ◽  
Graft Patency ◽  
Sprague Dawley ◽  
Rat Models ◽  
Vein Grafts ◽  
Sprague Dawley Rats ◽  
Training Courses ◽  
Vein Graft Failure

Background Torsion of vein grafts is a commonly cited reason for graft failure in clinical setting. Many microsurgery training courses have incorporated vein graft procedures in their curricula, and vein graft torsion is a common technical error made by the surgeons in these courses. To improve our understanding of the clinical reproducibility of practicing vein graft procedures in microsurgery training courses, this study aims to determine if torsion can lead to early vein graft failure in nonsurvival surgery rat models. Methods Sprague-Dawley rats were divided into five cohorts with five rats per cohort for a total of 25 rats. Cohorts were labeled based on degree of vein graft torsion (0, 45, 90, 135, and 180 degrees). Torsion was created in the vein grafts at the distal arterial end by mismatching sutures placed between the proximal end of the vein graft and the distal arterial end. Vein graft patency was then verified 2 and 24 hours postoperation. Results All vein grafts were patent 2 and 24 hours postoperation. At 2 hours, the average blood flow rate measurements for 0, 45, 90, 135, and 180 degrees of torsion were 0.37 ± 0.02, 0.38 ± 0.04, 0.34 ± 0.01, 0.33 ± 0.01, and 0.29 ± 0.02 mL/min, respectively. At 24 hours, they were 0.94 ± 0.07, 1.03 ± 0.15, 1.26 ± 0.22, 1.41 ± 0.11, and 0.89 ± 0.15 mL/min, respectively. Conclusion Torsion of up to 180 degrees does not affect early vein graft patency in rat models. To improve the clinical reproducibility of practicing vein graft procedures in rat models, we suggest that microsurgery instructors assess vein graft torsion prior to clamp release, as vessel torsion does not seem to affect graft patency once the clamps are removed.

scholarly journals Saphenous Vein Graft Disease Interventions

2021 ◽  
Vol 06 (03) ◽  
pp. 199-208
Author(s):  
Sarita Rao ◽  
K. Roshan Rao ◽  
Achukatla Kumar
Keyword(s):  
Saphenous Vein ◽  
Vein Graft ◽  
Left Internal Mammary Artery ◽  
Saphenous Vein Graft ◽  
Artery Bypass ◽  
Standard Of Care ◽  
Coronary Intervention ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Vein Grafts

AbstractIn the current era, coronary artery bypass grafting (CABG) is being increasingly performed using total arterial revascularization or a hybrid procedure of stenting of non-LAD disease and minimal access left internal mammary artery (LIMA) to LAD grafts, in order to minimize the need for vein grafts. Still, we encounter saphenous vein graft (SVG) disease, and it might require PCI, which often presents with unique challenges. The current favored strategy is to attempt PCI of the native coronary, if feasible, especially in long degenerated SVG disease, as it has shown better short- and long-term outcome. PCI is preferred over repeat CABG for early recurrent symptoms after CABG in patent LIMA graft and amenable anatomy patients. Balloon predilatation is not recommended unless delivery of an EPD or stent is not possible. Distal protection should be considered the standard of care for percutaneous coronary intervention (PCI) in most patients with older vein grafts, as periprocedural myocardial infarction and no reflow are the Achilles heel of SVG PCI. Intragraft vasodilators should be used liberally, even before balloon angioplasty/stenting. Avoid postdilatation, and usage of undersized but a longer stent length to reduce plaque extrusion through stent struts is preferred. Consider thrombectomy in lesions with a heavy thrombus burden. Keep activated clotting time on the higher side than in conventional PCI. Prolonged dual antiplatelet therapy (DAPT) based on the DAPT score is recommended. With all the precautions and care, we still need a fair wind in our favor to sail through the vein grafts disease.

Forearm Cephalic Vein Graft for Short, “Middle”-Flow, Internal Maxillary Artery to Middle Cerebral Artery Bypass

2015 ◽  
Vol 12 (2) ◽  
pp. 99-105 ◽  
Author(s):  
Erez Nossek ◽  
Peter D Costantino ◽  
David J Chalif ◽  
Rafael A Ortiz ◽  
Amir R Dehdashti ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Saphenous Vein ◽  
Vein Graft ◽  
Artery Bypass ◽  
Cephalic Vein ◽  
Maxillary Artery ◽  
Internal Maxillary Artery ◽  
Vein Grafts ◽  
Graft Length

Abstract BACKGROUND The cervical carotid system has been used as a source of donor vessels for radial artery or saphenous vein grafts in cerebral bypass. Recently, internal maxillary artery to middle cerebral artery bypass has been described as an alternative, with reduction of graft length potentially correlating with improved patency. OBJECTIVE To describe our experience using the forearm cephalic vein grafts for short segment internal maxillary artery to middle cerebral artery bypasses. METHODS All vein grafts were harvested from the volar forearm between the proximal cubital fossa where the median cubital vein is confluent with the cephalic vein and the distal wrist. RESULTS Six patients were treated with internal maxillary artery to middle cerebral artery bypass. In 4, the cephalic vein was used. Postoperative angiography demonstrated good filling of the grafts with robust distal flow. There were no upper extremity vascular complications. All but 1 patient (mortality) tolerated the procedure well. The other 3 patients returned to their neurological baseline with no new neurological deficit during follow-up. CONCLUSION The internal maxillary artery to middle cerebral artery “middle” flow bypass allows for shorter graft length with both the proximal and distal anastomoses within the same microsurgical field. These unique variable flow grafts represent an ideal opportunity for use of the cephalic vein of the forearm, which is more easily harvested than the wider saphenous vein graft and which has good match size to the M1/M2 segments of the middle cerebral artery. The vessel wall is supple, which facilitates handling during anastomosis. There is lower morbidity potential than utilization of the radial artery. Going forward, the cephalic vein will be our preferred choice for external carotid-internal carotid transplanted conduit bypass.

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.

Sign in / Sign up

Export Citation Format

Share Document