Preventing treatment failures in coronary artery disease: what can we learn from the biology of in-stent restenosis, vein graft failure, and internal thoracic arteries?

Abstract

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and the availability of percutaneous or surgical revascularization procedures significantly improves survival. However, both strategies are daunted by complications which limit long-term effectiveness. In-stent restenosis (ISR) is a major drawback for intracoronary stenting, while graft failure is the limiting factor for coronary artery bypass graft surgery (CABG), especially using veins. Conversely, internal thoracic artery (ITA) is known to maintain long-term patency in CABG. Understanding the biology and pathophysiology of ISR and vein graft failure (VGF) and mechanisms behind ITA resistance to failure is crucial to combat these complications in CAD treatment. This review intends to provide an overview of the biological mechanisms underlying stent and VGF and of the potential therapeutic strategy to prevent these complications. Interestingly, despite being different modalities of revascularization, mechanisms of failure of stent and saphenous vein grafts are very similar from the biological standpoint.

Exosomes derived from mesenchymal stem cells inhibit neointimal hyperplasia by activating the Erk1/2 signalling pathway in rats

“…Vascular injury is considered to be the main cause of neointimal hyperplasia initiation and progression [27]. Although current strategies to prevent restenosis are focused on the inhibition of neointimal hyperplasia through drugeluting stents and vascular brachytherapy, restenosis rates following endovascular intervention remain high [22,28]. Thus, it is important to understand the molecular mechanisms involved in neointima formation.…”

“…The pelleted exosomes were resuspended in 200 μL of phosphate buffered saline solution (PBS) and quantified by BCA protein assay kit (R33200, Thermo Fisher, USA). Exosomes were then assessed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA), as per previously described protocols [21,22]. Exosomes were further verified by western blot analysis of exosome-associated markers including CD81, CD63, HSP70, Calnexin and TSG101.…”

Outcome of endovascular recanalization for intracranial in-stent restenosis

“…We speculated the mechanism of re-ISR may be similar to that of ISR. Neointimal formation related to proliferation and migration of vascular smooth muscle cells may be a factor 43–46. It is often complicated by elastic recoil of the vessel wall after endovascular angioplasty.…”

Inflammatory Growth Factors and In-Stent Restenosis: Effect of Cytokines and Growth Factors

“…Recently, biological studies of ISR have shown that NF-kB/p65 pathway plays a significant role in the overexpression of VCAM-1 and E-selectin following stent implantation [103]. In human studies, it was found that, following a decrease in NF-kB/p65 translocation, the expression of VCAM-1, E-selectin, and endothelial cell activation also diminished dramatically.…”