Targeting Smad-Mediated TGFß Pathway in Coronary Artery Bypass Graft

Author(s):  
Marzuq A. Ungogo

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.

2000 ◽  
Vol 84 (11) ◽  
pp. 794-799 ◽  
Author(s):  
Annick Fiemeyer ◽  
Gilles Chatellier ◽  
Carine Chammas ◽  
Jean-François Baron ◽  
Martine Aiach ◽  
...  

SummaryPlatelet dysfunction can be a major factor in excessive bleeding following cardiopulmonary bypass (CBP). A rapid, specific and sensitive method to identify platelet dysfunction would be a useful tool for identifying patients at an increased risk of bleeding. The ability of PFA100™, an in vitro bleeding test, to predict increased bleeding risk linked to platelet dysfunction was tested in 146 patients undergoing primary coronary artery bypass graft. Blood samples were taken the day before surgery, and 15 min and 5 h after heparin neutralization. The preoperative closure times (CT), i. e. the time required for platelets in citrated whole blood to occlude an aperture cut into a membrane coated with collagen plus either epinephrine (CTEPI) or adenosine diphosphate (CTADP) were longer in blood-group-O patients than in patients with other groups. The 15 min postoperative values were significantly longer from preoperative values essentially owing to CBP-induced hemodilution. Interestingly, 5 h after CBP, a significant reduction in CT values probably reflected platelet hyperaggregability. No correlation was found between calculated blood loss (CBL) and either preoperative or postoperative PFA values.


Perfusion ◽  
2001 ◽  
Vol 16 (6) ◽  
pp. 511-518 ◽  
Author(s):  
Robert Groom ◽  
Joan Tryzelaar ◽  
Richard Forest ◽  
Kevin Niimi ◽  
Giovanni Cecere ◽  
...  

Early coronary artery bypass graft (CABG) failure is a troubling complication that may result in a wide range of problems, including refractory angina, myocardial infarction, low cardiac output, arrhythmia, and fatal heart failure. Early graft failures are related to poor quality and size of the distal native vascular bed, coagulation abnormalities, or technical problems involving the graft conduits and anastomoses. Unfortunately, graft failure is difficult to detect during surgery by visual assessment, palpation, or conventional monitoring. We evaluated the accuracy and utility of a transit-time, ultrasonic flow measurement system for measurement of CABGs. There were no differences between transit-time measurements and volumetric-time collected samples in an in vitro circuit over a range of flows from 10 to 100 ml/min (Bland and Altman Plot, 1.96 SD). Two hundred and ninety-eight CABGs were examined in 125 patients. Graft flow rate was proportional to the target vessel diameter. Nine technical errors were detected and corrected. Flow waveform morphology provided valuable information related to the quality of the anastamosis, which led to the immediate correction of technical problems at the time of surgery.


Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1619 ◽  
Author(s):  
Joanna Boguslawska ◽  
Piotr Kryst ◽  
Slawomir Poletajew ◽  
Agnieszka Piekielko-Witkowska

Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the “TGF-β paradox” in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.


Author(s):  
Andrew Mitchell ◽  
Giovanni Luigi De Maria ◽  
Adrian Banning

Most patients undergoing coronary artery bypass grafting, or CABG, in the past decade will have had a combination of arterial grafts and saphenous vein grafts (or received total arterial revascularization), as conduit patency for mammary arterial grafts has been shown to be significantly higher than that of vein grafts. This chapter covers one of the most common operations performed on patients with three-vessel coronary disease. It describes the role of pre-angiography, choosing an appropriate catheter, and the location of various grafts. It is fully illustrated with clinical images throughout, annotated to aid understanding.


2019 ◽  
Vol 17 (3) ◽  
pp. 155-169 ◽  
Author(s):  
Etem Caliskan ◽  
Domingos Ramos de Souza ◽  
Andreas Böning ◽  
Oliver J. Liakopoulos ◽  
Yeong-Hoon Choi ◽  
...  

2011 ◽  
Vol 14 (5) ◽  
pp. 291 ◽  
Author(s):  
Huishan Wang ◽  
Haibo Wu ◽  
Hui Jiang ◽  
Zengwei Wang ◽  
Evginij Potapov ◽  
...  

<p><b>Objective:</b> We aimed to investigate the initial experience of endoscopic vein harvesting (EVH) for coronary artery bypass grafting (CABG) in Chinese patients.</p><p><b>Methods:</b> Forty patients scheduled for isolated CABG were prospectively randomized into an EVH group (n = 20) and an open vein harvesting (OVH) group (n = 20). Clinical data were collected, and all of the vein grafts were assessed by macroscopic appearance, histologic quality (endothelial integrity), and functional characteristics of endothelial nitric oxide synthase.</p><p><b>Results:</b> The 2 groups were similar with respect to hospital mortality (EVH group, 0; OVH group, 1; <i>P</i> = 1). There were no postoperative myocardial infarctions in either group and no deaths or reinterventions in either group during the follow-up period. Harvesting times in the 2 groups were similar (EVH, 12.15 � 2.32 min; OVH, 12.55 � 2.11 min; <i>P</i> = .571). Three patients in the EVH group were converted to a partly open or skin-bridge technique. Electrocautery at least 2 mm distal to the origin of the side branch was the safety margin.</p><p><b>Conclusions:</b> The use of EVH in Chinese patients was not related to adverse events and may be safely used for CABG procedures. Preoperative duplex mapping, systemic heparinization before harvesting, minimal surgical manipulation, and sectioning of side branches at least 2 mm distal to the origin may help improve the quality of vein grafts harvested with EVH and maximize the benefit of this less-invasive technique.</p>


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