Endothelin‐1 and vein graft occlusion in patients undergoing bypass surgery

Abstract

The saphenous vein is the most commonly used graft for revascularization procedures in patients with coronary artery disease and critical limb ischaemia. However, the patency rate of this vessel is poor, with a high proportion of patients requiring further surgery. Early graft occlusion is caused by vasoconstriction or thrombus formation, with later stages of graft failure being due to neointimal formation or atherosclerosis. Apart from its potent constrictor action, endothelin-1 is also a potent proliferative and proinflammatory peptide that is implicated in a number of vascular diseases. The surgical trauma caused during preparation of the saphenous vein as a bypass graft stimulates the release of a number of factors affecting vascular reactivity and structure, including endothelin-1. Endothelin-1 not only constricts animal and human isolated saphenous vein segments but also causes vascular smooth muscle proliferation and neointimal thickening in vitro, actions that are mediated via endothelin (A and B) receptors. Experimentally, the effects of subtype-selective and dual receptor antagonists have been shown to inhibit endothelin-1-mediated constriction and cell proliferation of the saphenous vein. In this review, data supporting a role of endothelin-1 in vein graft occlusion are presented, and the therapeutic potential of endothelin receptor antagonists in improving graft performance is discussed.

Differential reactivity of human mammary artery and saphenous vein to prostaglandin E2: Implication for cardiovascular grafts

“…Moreover, in the years following CABG, patients are exposed to many other drugs that can potentially interfere with IMA and SV vascular reactivity as well as prostanoid biology. In addition, SV grafts undergo profound remodelling that compromise their long‐term viability (Dashwood, 2009; Jorapur et al ., 2009), and the underlying mechanisms are poorly understood. Given the complex biological roles of PGE 2 , and the fact that there is little or no information available concerning the effects of PGE 2 on the vascular tone of human IMA and SV, the aim of the present study was to compare these effects and to characterize the EP receptor subtypes implicated.…”

Endothelins and their receptors in cancer: Identification of therapeutic targets

“…Highly selective antagonists targeting either ET A R or ET B R, as well as ECE inhibitors, may prove useful in the clinical setting. The endothelin axis remains an interesting and active avenue of scientific endeavor, both in the cancer area and in other important pathological conditions [68]. …”

Oxidative Stress in Hypertensive Patients Induces an Increased Contractility in Vein Grafts Independent of Endothelial Function

“…Souza et al [ 29 ] have suggested that SV provides high graft patency. However, Dashwood has indicated that the patency rate is poor, with a high proportion of patients requiring further surgery [ 30 ]. The mechanisms involved in the patency of SV are unclear.…”

“…Xu et al [ 33 ] have observed increased reactivity to NE in mesenteric veins, and Li et al [ 14 ] have reported a hyperreactivity to endothelin-1 in the vena cava, which was related to the presence of oxidative stress. In human SV, hypertension stimulates endothelin-1 release, which not only affects vascular reactivity but also increases oxidative stress [ 30 ].…”