Inflammation in Vein Graft Disease

Abstract

Bypass surgery is one of the most frequently used strategies to revascularize tissues downstream occlusive atherosclerotic lesions. For venous bypass surgery the great saphenous vein is the most commonly used vessel. Unfortunately, graft efficacy is low due to the development of vascular inflammation, intimal hyperplasia and accelerated atherosclerosis. Moreover, failure of grafts leads to significant adverse outcomes and even mortality. The last couple of decades not much has changed in the treatment of vein graft disease (VGD). However, insight is the cellular and molecular mechanisms of VGD has increased. In this review, we discuss the latest insights on VGD and the role of inflammation in this. We discuss vein graft pathophysiology including hemodynamic changes, the role of vessel wall constitutions and vascular remodeling. We show that profound systemic and local inflammatory responses, including inflammation of the perivascular fat, involve both the innate and adaptive immune system.

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

“…The balance of the number of different immune cell types and their activation levels is crucial for health and disease. Overwhelming evidence has associated chronic inflammation with various pathological conditions and their potential causes, including atherosclerosis, cardiovascular events, cancer, autoimmune diseases, metabolic disorders, neurological diseases, and aging (Johnston et al 1987;Gisterå and Hansson 2017;Tabas and Lichtman 2017;de Vries and Quax 2018;Gomez et al 2018;Aday and Ridker 2019;Bercovici et al 2019;Di Benedetto et al 2019;Guner and Kim 2019;Horwitz et al 2019;O'Rourke et al 2019;Othman et al 2019;Trott and Fadel 2019). Many investigations have focused on the major role of macrophages in such contexts and mechanisms for their proinflammatory activation (Murray and Wynn 2011;Wynn and Vannella 2016;Gisterå and Hansson 2017;Tabas and Lichtman 2017;Decano and Aikawa 2018;Funes et al 2018;Swirski and Nahrendorf 2018;O'Rourke et al 2019).…”

Pro-resolving lipid mediators in vascular disease

“…Vascular injury and intimal hyperplasia. In settings of acute vessel injury such as angioplasty or bypass grafting, loss of endothelial integrity and damage to underlying VSMCs initiates a rapid response of platelets, coagulation proteins, and leukocytes, particularly neutrophils and monocytes (34)(35)(36)38). These elements attach to and invade the vessel wall, elaborating an array of growth factors, proteases, cytokines, and vasoactive substances that induce secondary proinflammatory gene cascades in the surviving VSMCs and adventitial cells.…”

“…Surgical interventions for advanced PAD, such as angioplasty, stent placement, and bypass surgery, superimpose acute vascular injury on this chronic inflammatory substrate. The magnitude as well as temporal and spatial distribution of the ensuing inflammatory response in the vessel wall, and its resolution, are key drivers of vessel remodeling and downstream clinical outcomes (34)(35)(36)(37)(38). While often technically successful, the long-term outcomes of such procedures are limited by excessive vessel scarring or "restenosis" that may affect 50% or more of patients within 2 to 3 years (39)(40)(41).…”

Saphenous vein graft disease, pathophysiology, prevention, and treatment. A review of the literature

“…Like the native artery atherosclerosis, the vein graft atherosclerosis can suffer plaque rupture and AT, which has been described in necropsy samples 25 . However, the vein graft atherosclerosis tends to be diffuse, concentric, and friable with a poorly developed or absent fibrous cap and little evidence of calcification, making it more prone to rupture than native artery atherosclerotic plaques 6,18,26,27 …”

“…After the initial denudation, new ECs can be seen as early as the first week after surgery in experimental models, however, after the endothelium is restored the process of IH does not reverse, this is thought to be in part due to the increase of shear stress on the wall which makes the new endothelium dysfunctional and partly due to the now chronic localized inflammatory response 5,11,18 …”