The Role of Endothelial Cells in the Onset, Development and Modulation of Vein Graft Disease

Abstract

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. Given the importance of these cells in maintaining a healthy haemodynamic environment, dysfunction of the endothelium is central to a host of vascular diseases and is a key predictor of cardiovascular risk. Of note, 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. This review aims to provide an overview of the current working knowledge regarding the role of endothelial cells in the onset, development, and modulation of vein graft disease, as well as addressing current surgical and medical management approaches which aim to beneficially modulate endothelial function and improve patient outcomes.

Osteopontin Activation and Microcalcification in Venous Grafts Can Be Modulated by Dexamethasone

“…The LSV remains the most used conduit for CABG which can be due to the ease of harvest, ability to obtain long length for multiple grafting, and because clinical trials using arterial grafting have not produced consistent results demonstrating long-term superiority [27,28]. The use of LSV is complicated by high rates of restenosis or occlusion, broadly termed vein graft failure, due to the development of IH which is a complex process that is triggered almost immediately once the vein is harvested and is related to the activation of multitude of inflammatory pathways [7,19,20].…”

“…It is recognised that up to 40% of vein grafts occlude within 10 years of surgery, with estimated attrition rates of 1% to 2% per year between 1 and 6 years, and 4% per year between 6 and 10 years [5,6]. IH occurs because of chronic structural changes in vein grafts due to the abnormal migration and proliferation of smooth muscle cells (SMCs), accompanied by an increase in the amount of extracellular matrix (ECM) [7,8]. IH is a multifactorial process that starts during the harvesting of veins and is known to result in the activation of endothelial cells (EC) [7].…”

“…IH occurs because of chronic structural changes in vein grafts due to the abnormal migration and proliferation of smooth muscle cells (SMCs), accompanied by an increase in the amount of extracellular matrix (ECM) [7,8]. IH is a multifactorial process that starts during the harvesting of veins and is known to result in the activation of endothelial cells (EC) [7]. ECs are further activated by the sudden exposure to new mechanical forces in the arterial circulation, such as distension and shear stress, via the activation of different signalling pathways such as mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-KB) [8][9][10].…”

Bacterial-Nanocellulose-Based Biointerfaces and Biomimetic Constructs for Blood-Contacting Medical Applications

“…28,32 Blood vessels are made up of three layers: (1) tunica externa (outer layer) which provides structural support, (2) tunica media (middle layer) which contains elastic and muscular tissue allowing for a change in diameter of the vessel during flow, and (3) tunica intima (inner layer) which contains a smooth endothelial layer that provides the vessel's innate anticoagulant properties. 33 All three of these layers are important in designing and developing tissue engineered biomaterials for use as a vascular graft. Successful endothelization of the tunica intima decreases thrombogenicity, 34 and matching the mechanical properties of the biomaterial to the tunica media and tunica externa prevents compliance mismatch which has been found to lead to intimal hyperplasia.…”

“…Blood vessels are made up of three layers: (1) tunica externa (outer layer) which provides structural support, (2) tunica media (middle layer) which contains elastic and muscular tissue allowing for a change in diameter of the vessel during flow, and (3) tunica intima (inner layer) which contains a smooth endothelial layer that provides the vessel’s innate anticoagulant properties . All three of these layers are important in designing and developing tissue engineered biomaterials for use as a vascular graft.…”